RESUMEN
Aortic dissection (AD), caused by tearing of the intima and avulsion of the aortic media, is a severe threat to patient life and organ function. Iron is closely related to dissection formation and organ injury, but the mechanism of iron ion transport disorder in endothelial cells (ECs) remains unclear. We identified the characteristic EC of dissection with iron overload by single-cell RNA sequencing data. After intersecting iron homeostasis and differentially expressed genes, it was found that hypoxia-inducible factor-1α (HIF-1α) and divalent metal transporter 1 (DMT1) are key genes for iron ion disorder. Subsequently, IL-6R was identified as an essential reason for the JAK-STAT activation, a classical iron regulation pathway, through further intersection and validation. In in vivo and in vitro, both high IL-6 receptor expression and elevated IL-6 levels promote JAK1-STAT3 phosphorylation, leading to increased HIF-1α protein levels. Elevated HIF-1α binds explicitly to the 5'-UTR sequence of the DMT1 gene and transcriptionally promotes DMT1 expression, thereby increasing Fe2+ accumulation and endoplasmic reticulum stress (ERS). Blocking IL-6R and free iron with deferoxamine and tocilizumab significantly prolonged survival and reduced aortic and organ damage in dissection mice. A comparison of perioperative data between AD patients and others revealed that high free iron, IL-6, and ERS levels are characteristics of AD patients and are correlated with prognosis. In conclusion, activated IL-6/JAK1/STAT3 signaling axis up-regulates DMT1 expression by increasing HIF-1α, thereby increasing intracellular Fe2+ accumulation and tissue injury, which suggests a potential therapeutic target for AD.
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Disección Aórtica , Proteínas de Transporte de Catión , Células Endoteliales , Interleucina-6 , Sobrecarga de Hierro , Transducción de Señal , Animales , Interleucina-6/metabolismo , Proteínas de Transporte de Catión/metabolismo , Proteínas de Transporte de Catión/genética , Ratones , Células Endoteliales/metabolismo , Humanos , Disección Aórtica/metabolismo , Sobrecarga de Hierro/metabolismo , Masculino , Ratones Endogámicos C57BL , Factor de Transcripción STAT3/metabolismo , Regulación hacia Arriba , Hierro/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/genéticaRESUMEN
Succinic acid (SA), a dicarboxylic acid of industrial importance, can be efficiently produced by metabolically engineered Mannheimia succiniciproducens. Although the importance of magnesium (Mg2+) ion on SA production has been evident from our previous studies, the role of Mg2+ ion remains largely unexplored. In this study, we investigated the impact of Mg2+ ion on SA production and developed a hyper-SA producing strain of M. succiniciproducens by reconstructing the Mg2+ ion transport system. To achieve this, optimal alkaline neutralizer comprising Mg2+ ion was developed and the physiological effect of Mg2+ ion was analyzed. Subsequently, the Mg2+ ion transport system was reconstructed by introducing an efficient Mg2+ ion transporter from Salmonella enterica. A high-inoculum fed-batch fermentation of the final engineered strain produced 152.23 ± 0.99 g/L of SA, with a maximum productivity of 39.64 ± 0.69 g/L/h. These findings highlight the importance of Mg2+ ions and transportation system optimization in succinic acid production by M. succiniciproducens.
Asunto(s)
Fermentación , Magnesio , Mannheimia , Ácido Succínico , Ácido Succínico/metabolismo , Magnesio/metabolismo , Mannheimia/metabolismo , Mannheimia/genética , Ingeniería Metabólica/métodos , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Proteínas de Transporte de Catión/metabolismo , Proteínas de Transporte de Catión/genéticaRESUMEN
Thyroid cancer is the most frequently observed endocrine-related malignancy among which anaplastic thyroid cancer (ATC) is the most fatal subtype. The synthesis of protein is active to satisfy the rapid growth of ATC tumor, but the mechanisms regulating protein synthesis are still unknown. Our research revealed that kinetochore protein NUF2 played an essential role in protein synthesis and drove the progression of ATC. The prognosis of patients with thyroid carcinoma was positively correlated with high NUF2 expression. Depletion of NUF2 in ATC cells notably inhibited the proliferation and induced apoptosis, while overexpression of NUF2 facilitated ATC cell viability and colony formation. Deletion of NUF2 significantly suppressed the growth and metastasis of ATC in vivo. Notably, knockdown of NUF2 epigenetically inhibited the expression of magnesium transporters through reducing the abundance of H3K4me3 at promoters, thereby reduced intracellular Mg2+ concentration. Furthermore, we found the deletion of NUF2 or magnesium transporters significantly inhibited the protein synthesis mediated by the PI3K/Akt/mTOR pathway. In conclusion, NUF2 functions as an emerging regulator for protein synthesis by maintaining the homeostasis of intracellular Mg2+, which finally drives ATC progression.
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Progresión de la Enfermedad , Homeostasis , Magnesio , Carcinoma Anaplásico de Tiroides , Animales , Femenino , Humanos , Ratones , Apoptosis , Proteínas de Transporte de Catión/metabolismo , Proteínas de Transporte de Catión/genética , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Línea Celular Tumoral , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Magnesio/metabolismo , Ratones Desnudos , Biosíntesis de Proteínas , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Carcinoma Anaplásico de Tiroides/metabolismo , Carcinoma Anaplásico de Tiroides/patología , Carcinoma Anaplásico de Tiroides/genética , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/metabolismo , Neoplasias de la Tiroides/genética , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
Neonatal iron deficiency anemia is prevalent among domestic pigs but does not occur in the offspring of wild boar. The main causes of this disorder in piglets of modern pig breeds are paucity of hepatic iron stores, high birth weight, and rapid growth. Replenishment of fetal iron stores is a direct result of iron transfer efficiency across the placenta. In this study, we attempted to investigate the molecular potential of iron transfer across the placenta as a possible cause of differences between wild boar and Polish Large White (PLW) offspring. Furthermore, by analyzing placentas from PLW gilts that had litters of different sizes, we aimed to elucidate the impact of the number of fetuses on placental ability to transport iron. Using RNA sequencing, we examined the expression of iron-related genes in the placentas from wild boar and PLW gilts. We did not reveal significant differences in the expression of major iron transporters among all analyzed placentas. However, in wild boar placentas, we found higher expression of copper-dependent ferroxidases such as ceruloplasmin, zyklopen, and hephaestin, which facilitate iron export to the fetal circulation. We also determined a close co-localization of ceruloplasmin and zyklopen with ferroportin, the only iron exporter.
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Hierro , Tamaño de la Camada , Placenta , Sus scrofa , Animales , Femenino , Placenta/metabolismo , Hierro/metabolismo , Embarazo , Sus scrofa/metabolismo , Sus scrofa/genética , Porcinos , Ceruloplasmina/metabolismo , Ceruloplasmina/genética , Proteínas de Transporte de Catión/metabolismo , Proteínas de Transporte de Catión/genética , Transporte BiológicoRESUMEN
Iron is a vital element involved in a plethora of metabolic activities. Mammalian systemic iron homeostasis is mainly modulated by hepcidin, the synthesis of which is regulated by a number of proteins, including the hemochromatosis-associated proteins Hfe and Transferrin Receptor 2 (TfR2). Macrophages play versatile functions in iron homeostasis by storing iron derived from the catabolism of erythrocytes and supplying iron required for erythropoiesis. The absence of Hfe in macrophages causes a mild iron deficiency in aged mice and leads to an overproduction of the iron exporter Ferroportin 1 (Fpn1). Conversely, TfR2 gene silencing in macrophages does not influence systemic iron metabolism but decreases transcription of the macrophage Fpn1 in adult mice and modulates their immune response. This study investigated cellular and systemic iron metabolism in adult and aged male mice with macrophage-specific Hfe and TfR2 silencing (double knock-out, DKO). Serum iron parameters were significantly modified in aged animals, and significant differences were found in hepatic hepcidin transcription at both ages. Interestingly, splenic iron content was low in adult DKOs and splenic Fpn1 transcription was significantly increased in DKO animals at both ages, while the protein amount does not reflect the transcriptional trend. Additionally, DKO macrophages were isolated from mice bone marrow (BMDMs) and showed significant variations in the transcription of iron genes and protein amounts in targeted mice compared to controls. Specifically, Tranferrin Receptor 1 (TfR1) increased in DKO adult mice BMDMs, while the opposite is observed in the cells of aged DKO mice. Fpn1 transcript was significantly decreased in the BMDMs of adult DKO mice, while the protein was reduced at both ages. Lastly, a significant increase in Erythropoietin production was evidenced in aged DKO mice. Overall, our study reveals that Hfe and TfR2 in macrophages regulate hepatic Hepc production and affect iron homeostasis in the spleen and BMDMs, leading to an iron deficiency in aged animals that impairs their erythropoiesis.
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Proteína de la Hemocromatosis , Hierro , Macrófagos , Ratones Noqueados , Receptores de Transferrina , Bazo , Animales , Receptores de Transferrina/metabolismo , Receptores de Transferrina/genética , Bazo/metabolismo , Hierro/metabolismo , Macrófagos/metabolismo , Ratones , Masculino , Proteína de la Hemocromatosis/genética , Proteína de la Hemocromatosis/metabolismo , Médula Ósea/metabolismo , Proteínas de Transporte de Catión/metabolismo , Proteínas de Transporte de Catión/genética , Hepcidinas/metabolismo , Hepcidinas/genética , Ratones Endogámicos C57BL , Homeostasis , Hígado/metabolismoRESUMEN
BACKGROUND: The KT/HAK/KUP is the largest K+ transporter family in plants, playing crucial roles in K+ absorption, transport, and defense against environmental stress. Sweet watermelon is an economically significant horticultural crop belonging to the genus Citrullus, with a high demand for K+ during its growth process. However, a comprehensive analysis of the KT/HAK/KUP gene family in watermelon has not been reported. RESULTS: 14 KT/HAK/KUP genes were identified in the genomes of each of seven Citrullus species. These KT/HAK/KUPs in watermelon were unevenly distributed across seven chromosomes. Segmental duplication is the primary driving force behind the expansion of the KT/HAK/KUP family, subjected to purifying selection during domestication (Ka/Ks < 1), and all KT/HAK/KUPs exhibit conserved motifs and could be phylogenetically classified into four groups. The promoters of KT/HAK/KUPs contain numerous cis-regulatory elements related to plant growth and development, phytohormone response, and stress response. Under K+ deficiency, the growth of watermelon seedlings was significantly inhibited, with cultivated watermelon experiencing greater impacts (canopy width, redox enzyme activity) compared to the wild type. All KT/HAK/KUPs in C. lanatus and C. amarus exhibit specific expression responses to K+-deficiency and drought stress by qRT-PCR. Notably, ClG42_07g0120700/CaPI482276_07g014010 were predominantly expressed in roots and were further induced by K+-deficiency and drought stress. Additionally, the K+ transport capacity of ClG42_07g0120700 under low K+ stress was confirmed by yeast functional complementation assay. CONCLUSIONS: KT/HAK/KUP genes in watermelon were systematically identified and analyzed at the pangenome level and provide a foundation for understanding the classification and functions of the KT/HAK/KUPs in watermelon plants.
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Citrullus , Sequías , Filogenia , Proteínas de Plantas , Estrés Fisiológico , Citrullus/genética , Citrullus/metabolismo , Citrullus/crecimiento & desarrollo , Estrés Fisiológico/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Potasio/metabolismo , Regulación de la Expresión Génica de las Plantas , Genoma de Planta , Familia de Multigenes , Proteínas de Transporte de Catión/genética , Proteínas de Transporte de Catión/metabolismo , Deficiencia de Potasio/genética , Deficiencia de Potasio/metabolismo , Regiones Promotoras GenéticasRESUMEN
OBJECTIVE: Nowadays, the prevalence of cognitive impairment in women has gradually increased, especially in postmenopausal women. There were few studies on the mechanistic effects of iron exposure on neurotoxicity in postmenopausal women. The aim of this study is to investigate the effect of iron accumulation on cognitive ability in ovariectomized mice and its possible mechanism and to provide a scientific basis for the prevention of cognitive dysfunction in postmenopausal women. METHODS: Female C57BL/6N ovariectomized model mice were induced with ferric citrate (FAC). The mice were randomly divided into 5 groups: control, sham, ovariectomized (Ovx), Ovx + 50 mg/kg FAC (Ovx + l), and Ovx + 100 mg/kg FAC (Ovx + h). The impact of motor and cognitive function was verified by a series of behavioral tests. The levels of serum iron parameters, malondialdehyde, and superoxide dismutase were measured. The ultrastructure of mice hippocampal microglia was imaged by transmission electron microscopy. The differential expression of hippocampal proteins was analyzed by Tandem Mass Tag labeling. RESULTS: Movement and cognitive function in Ovx + l/Ovx + h mice were significantly decreased compared to control and Sham mice. Then, iron exposure caused histopathological changes in the hippocampus of mice. In addition, proteomic analysis revealed that 29/27/41 proteins were differentially expressed in the hippocampus when compared by Ovx vs. Sham, Ovx + l vs. Ovx, as well as Ovx + h vs. Ovx + l groups, respectively. Moreover, transferrin receptor protein (TFR1) and divalent metal transporter 1 (DMT1) protein expression were significantly increased in the iron accumulation mice model with ovariectomy. CONCLUSION: Iron exposure could cause histopathological damage in the hippocampus of ovariectomised mice and, by altering hippocampal proteomics, particularly the expression of hippocampal iron metabolism-related proteins, could further influence cognitive impairment in ovariectomized mice.
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Modelos Animales de Enfermedad , Compuestos Férricos , Hipocampo , Hierro , Ratones Endogámicos C57BL , Ovariectomía , Animales , Femenino , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Hipocampo/patología , Ratones , Hierro/metabolismo , Compuestos Férricos/toxicidad , Compuestos Férricos/farmacología , Aprendizaje por Laberinto/efectos de los fármacos , Disfunción Cognitiva/metabolismo , Trastornos del Conocimiento/patología , Trastornos del Conocimiento/inducido químicamente , Superóxido Dismutasa/metabolismo , Proteínas de Transporte de Catión/metabolismo , Receptores de Transferrina/metabolismoRESUMEN
Activating Ca2+-sensitive enzymes of oxidative metabolism while preventing calcium overload that leads to mitochondrial and cellular injury requires dynamic control of mitochondrial Ca2+ uptake. This is ensured by the mitochondrial calcium uptake (MICU)1/2 proteins that gate the pore of the mitochondrial calcium uniporter (mtCU). MICU1 is relatively sparse in the heart, and recent studies claimed the mammalian heart lacks MICU1 gating of mtCU. However, genetic models have not been tested. We find that MICU1 is present in a complex with MCU in nonfailing human hearts. Furthermore, using murine genetic models and pharmacology, we show that MICU1 and MICU2 control cardiac mitochondrial Ca2+ influx, and that MICU1 deletion alters cardiomyocyte mitochondrial calcium signaling and energy metabolism. MICU1 loss causes substantial compensatory changes in the mtCU composition and abundance, increased turnover of essential MCU regulator (EMRE) early on and, later, of MCU, that limit mitochondrial Ca2+ uptake and allow cell survival. Thus, both the primary consequences of MICU1 loss and the ensuing robust compensation highlight MICU1's relevance in the beating heart.
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Señalización del Calcio , Proteínas de Unión al Calcio , Calcio , Proteínas de Transporte de Catión , Proteínas de Transporte de Membrana Mitocondrial , Miocitos Cardíacos , Animales , Proteínas de Unión al Calcio/metabolismo , Proteínas de Unión al Calcio/genética , Ratones , Proteínas de Transporte de Membrana Mitocondrial/metabolismo , Proteínas de Transporte de Membrana Mitocondrial/genética , Humanos , Proteínas de Transporte de Catión/metabolismo , Proteínas de Transporte de Catión/genética , Miocitos Cardíacos/metabolismo , Señalización del Calcio/fisiología , Calcio/metabolismo , Mitocondrias Cardíacas/metabolismo , Canales de Calcio/metabolismo , Canales de Calcio/genética , Ratones Noqueados , Miocardio/metabolismo , MasculinoRESUMEN
SLC30A9 (ZnT9) is a mitochondria-resident zinc transporter. Mutations in SLC30A9 have been reported in human patients with a novel cerebro-renal syndrome. Here, we show that ZnT9 is an evolutionarily highly conserved protein, with many regions extremely preserved among evolutionarily distant organisms. In Drosophila melanogaster (the fly), ZnT9 (ZnT49B) knockdown results in acutely impaired movement and drastic mitochondrial deformation. Severe Drosophila ZnT9 (dZnT9) reduction and ZnT9-null mutant flies are pupal lethal. The phenotype of dZnT9 knockdown can be partially rescued by mouse ZnT9 expression or zinc chelator TPEN, indicating the defect of dZnT9 loss is indeed a result of zinc dyshomeostasis. Interestingly, in the mouse, germline loss of Znt9 produces even more extreme phenotypes: the mutant embryos exhibit midgestational lethality with severe development abnormalities. Targeted mutagenesis of Znt9 in the mouse brain leads to serious dwarfism and physical incapacitation, followed by death shortly. Strikingly, the GH/IGF-1 signals are almost non-existent in these tissue-specific knockout mice, consistent with the medical finding in some human patients with severe mitochondrial deficiecny. ZnT9 mutations cause mitochondrial zinc dyshomeostasis, and we demonstrate mechanistically that mitochondrial zinc elevation quickly and potently inhibits the activities of respiration complexes. These results reveal the critical role of ZnT9 and mitochondrial zinc homeostasis in mammalian development. Based on our functional analyses, we finally discussed the possible nature of the so far identified human SLC30A9 mutations.
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Proteínas de Transporte de Catión , Desarrollo Embrionario , Mitocondrias , Zinc , Animales , Proteínas de Transporte de Catión/metabolismo , Proteínas de Transporte de Catión/genética , Humanos , Zinc/metabolismo , Ratones , Mitocondrias/metabolismo , Desarrollo Embrionario/genética , Drosophila melanogaster/metabolismo , Drosophila melanogaster/genética , Drosophila melanogaster/embriología , Evolución Molecular , Ratones Noqueados , Secuencia de Aminoácidos , Proteínas Mitocondriales/metabolismo , Proteínas Mitocondriales/genética , Factores de Transcripción , Proteínas de Ciclo CelularRESUMEN
The present study aimed to investigate the occurrence of ferroptosis in mouse hippocampal tissue and changes in related pathways after exposure to high-altitude hypoxia. A low-pressure hypoxia model was established using a high-altitude environment at 4 010 m. HE staining was used to observe morphological changes in mouse hippocampal tissue, immunohistochemical staining was used to observe lipid peroxidation levels in hippocampal tissue, and corresponding kits were used to measure malondialdehyde (MDA), reduced glutathione (GSH), and Fe2+ levels in hippocampal tissue. Western blot was used to detect glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), ferritin heavy chain 1 (FTH1), ferroportin 1 (FPN1), transferrin receptor 1 (TfR1), ferroptosis suppressor protein 1 (FSP1), and acyl-CoA synthase long chain family member 4 (ACSL4). The results showed that, compared with the plain control group, the mice exposed to high-altitude hypoxia for 1, 3, 7, and 14 d exhibited significant pathological damage, disordered arrangement, and obvious nuclear condensation in the dentate gyrus of the hippocampus. Compared with the plain control group, high-altitude hypoxia exposure increased 4-hydroxynonenal (4-HNE) content in the dentate gyrus and hippocampal MDA content, whereas significantly decreased hippocampal GSH content. Compared with the plain control group, the Fe2+ content in the hippocampus of mice exposed to high-altitude hypoxia for 14 d significantly increased. Compared with the plain control group, the protein expression levels of GPX4, FTH1, FPN1, TfR1, and FSP1 in the hippocampus of mice exposed to high-altitude hypoxia were significantly down-regulated (SLC7A11 was significantly down-regulated only in the 7-d high-altitude hypoxia exposure group), while the protein expression level of ACSL4 was only significantly up-regulated in the 14-d high-altitude hypoxia exposure group. These results suggest that exposure to high-altitude hypoxia for 14 d can reduce GSH synthesis in mouse hippocampus, down-regulate GPX4 expression, lead to GSH metabolism disorders, inhibit iron storage and efflux, promote lipid peroxidation reaction, and inhibit CoQ10H2's anti-lipid peroxidation effect, ultimately leading to ferroptosis.
Asunto(s)
Mal de Altura , Ferroptosis , Hipocampo , Hipoxia , Animales , Ferroptosis/fisiología , Hipocampo/metabolismo , Ratones , Hipoxia/metabolismo , Hipoxia/fisiopatología , Masculino , Mal de Altura/metabolismo , Mal de Altura/fisiopatología , Peroxidación de Lípido , Receptores de Transferrina/metabolismo , Altitud , Fosfolípido Hidroperóxido Glutatión Peroxidasa/metabolismo , Glutatión/metabolismo , Malondialdehído/metabolismo , Hierro/metabolismo , Proteínas de Transporte de Catión/metabolismo , Sistema de Transporte de Aminoácidos y+/metabolismo , Sistema de Transporte de Aminoácidos y+/genéticaRESUMEN
Understanding the role of iron in ethanol-derived hepatic stress could help elucidate the efficacy of dietary or clinical interventions designed to minimize liver damage from chronic alcohol consumption. We hypothesized that normal levels of iron are involved in ethanol-derived liver damage and reduced dietary iron intake would lower the damage caused by ethanol. We used a pair-fed mouse model utilizing basal Lieber-DeCarli liquid diets for 22 weeks to test this hypothesis. In our mouse model, chronic ethanol exposure led to mild hepatic stress possibly characteristic of early-stage alcoholic liver disease, seen as increases in liver-to-body weight ratios. Dietary iron restriction caused a slight decrease in non-heme iron and ferritin (FeRL) expression while it increased transferrin receptor 1 (TfR1) expression without changing ferroportin 1 (FPN1) expression. It also elevated protein lysine acetylation to a more significant level than in ethanol-fed mice under normal dietary iron conditions. Interestingly, iron restriction led to an additional reduction in nicotinamide adenine dinucleotide (NAD+) and NADH levels. Consistent with this observation, the major mitochondrial NAD+-dependent deacetylase, NAD-dependent deacetylase sirtuin-3 (SIRT3), expression was significantly reduced causing increased protein lysine acetylation in ethanol-fed mice at normal and low-iron conditions. In addition, the detection of superoxide dismutase 1 and 2 levels (SOD1 and SOD2) and oxidative phosphorylation (OXPHOS) complex activities allowed us to evaluate the changes in antioxidant and energy metabolism regulated by ethanol consumption at normal and low-iron conditions. We observed that the ethanol-fed mice had mild liver damage associated with reduced energy and antioxidant metabolism. On the other hand, iron restriction may exacerbate certain activities of ethanol further, such as increased protein lysine acetylation and reduced antioxidant metabolism. This metabolic change may prove a barrier to the effectiveness of dietary reduction of iron intake as a preventative measure in chronic alcohol consumption.
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Antioxidantes , Metabolismo Energético , Etanol , Animales , Ratones , Acetilación/efectos de los fármacos , Metabolismo Energético/efectos de los fármacos , Antioxidantes/metabolismo , Masculino , Hierro/metabolismo , Superóxido Dismutasa-1/metabolismo , Superóxido Dismutasa-1/genética , Superóxido Dismutasa/metabolismo , Lisina/metabolismo , Hígado/metabolismo , Hígado/efectos de los fármacos , Receptores de Transferrina/metabolismo , Sirtuina 3/metabolismo , Sirtuina 3/genética , NAD/metabolismo , Ferritinas/metabolismo , Proteínas de Transporte de Catión/metabolismo , Proteínas de Transporte de Catión/genética , Estrés Oxidativo/efectos de los fármacos , Ratones Endogámicos C57BL , Hepatopatías Alcohólicas/metabolismo , Hepatopatías Alcohólicas/patología , Hepatopatías Alcohólicas/etiologíaAsunto(s)
Proteínas de Transporte de Catión , Hepcidinas , Ubiquitina-Proteína Ligasas , Humanos , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/genética , Hepcidinas/metabolismo , Hepcidinas/genética , Células HeLa , Proteínas de Transporte de Catión/metabolismo , Proteínas de Transporte de Catión/genética , Proteolisis , UbiquitinaciónRESUMEN
Arbuscular mycorrhizal (AM) fungi are well known for enhancing phosphorus uptake in plants; however, their regulating roles in cation transporting gene family, such as natural resistance-associated macrophage protein (NRAMP), are still limited. Here, we performed bioinformatics analysis and quantitative expression assays of tomato SlNRAMP 1 to 5 genes under nutrient deficiency and cadmium (Cd) stress in response to AM symbiosis. These five SlNRAMP members are mainly located in the plasma or vacuolar membrane and can be divided into two subfamilies. Cis-element analysis revealed several motifs involved in phytohormonal and abiotic regulation in their promoters. SlNRAMP2 was downregulated by iron deficiency, while SlNRAMP1, SlNRAMP3, SlNRAMP4, and SlNRAMP5 responded positively to copper-, zinc-, and manganese-deficient conditions. AM colonization reduced Cd accumulation and expression of SlNRAMP3 but enhanced SlNRAMP1, SlNRAMP2, and SlNRMAP4 in plants under Cd stress. These findings provide valuable genetic information for improving tomato resilience to nutrient deficiency and heavy metal stress by developing AM symbiosis.
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Cadmio , Regulación de la Expresión Génica de las Plantas , Micorrizas , Proteínas de Plantas , Solanum lycopersicum , Estrés Fisiológico , Simbiosis , Micorrizas/fisiología , Solanum lycopersicum/microbiología , Solanum lycopersicum/genética , Solanum lycopersicum/metabolismo , Cadmio/toxicidad , Cadmio/metabolismo , Simbiosis/genética , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Estrés Fisiológico/genética , Proteínas de Transporte de Catión/genética , Proteínas de Transporte de Catión/metabolismoAsunto(s)
Deficiencia de Magnesio , Magnesio , Humanos , Magnesio/sangre , Magnesio/metabolismo , Magnesio/uso terapéutico , Deficiencia de Magnesio/sangre , Deficiencia de Magnesio/diagnóstico , Deficiencia de Magnesio/tratamiento farmacológico , Deficiencia de Magnesio/genética , Literatura de Revisión como Asunto , Riñón/metabolismo , Riñón/fisiopatología , Proteínas de Transporte de Catión/genética , Proteínas de Transporte de Catión/metabolismo , Absorción Intestinal , Síndrome del Intestino Corto/complicaciones , Síndrome del Intestino Corto/metabolismo , Síndrome del Intestino Corto/fisiopatologíaAsunto(s)
Deficiencia de Magnesio , Magnesio , Femenino , Humanos , Proteínas de Transporte de Catión/genética , Proteínas de Transporte de Catión/metabolismo , Absorción Intestinal , Riñón/metabolismo , Riñón/fisiopatología , Magnesio/sangre , Magnesio/metabolismo , Magnesio/uso terapéutico , Deficiencia de Magnesio/sangre , Deficiencia de Magnesio/diagnóstico , Deficiencia de Magnesio/tratamiento farmacológico , Deficiencia de Magnesio/genética , Literatura de Revisión como Asunto , Síndrome del Intestino Corto/sangre , Síndrome del Intestino Corto/complicaciones , Síndrome del Intestino Corto/fisiopatologíaRESUMEN
Soybean is one of the most important crops for producing high quality oil and protein. Mineral nutrient deficiencies are frequently observed in soybeans. However, there are few studies to understand the absorption process of mineral nutrients in soybeans. Here, we investigated the functions of soybean (Glycine max L.) IRT1.1 (IRON-REGULATED TRANSPORTER 1.1) in the transportation of mineral elements. Heterologous expression of GmIRT1.1 in yeast mutants revealed that GmIRT1.1 compensated for the growth defects of Δfet3fet4 and Δsmf1 mutants under iron (Fe) and manganese (Mn) deficiency conditions, respectively, and enhanced the sensitivity of the Δycf1 mutant to cadmium (Cd) toxicity. Expression analysis revealed that GmIRT1.1 was only significantly induced by Fe deficiency and was primarily expressed in roots. Furthermore, the GmIRT1.1 overexpression lines enhanced Arabidopsis tolerance to Fe deficiency, leading to increased accumulation of Fe in the roots and shoots. Additionally, the transgenic lines increased the sensitivity to Mn and Cd toxicity. Subcellular localization analysis revealed that GmIRT1.1 was localized on the plasma membrane. Moreover, the results obtained from the soybean hairy roots system indicated that the localization of GmIRT1.1 was dependent on the regulation of Fe homeostasis in plant. Consequently, these results suggested that GmIRT1.1 was responsible for the transportation of Fe, Mn and Cd.
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Arabidopsis , Cadmio , Glycine max , Hierro , Manganeso , Proteínas de Plantas , Plantas Modificadas Genéticamente , Glycine max/genética , Glycine max/metabolismo , Manganeso/metabolismo , Hierro/metabolismo , Cadmio/metabolismo , Cadmio/toxicidad , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Transporte Biológico , Regulación de la Expresión Génica de las Plantas , Raíces de Plantas/metabolismo , Raíces de Plantas/genética , Proteínas de Transporte de Catión/metabolismo , Proteínas de Transporte de Catión/genética , Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/genéticaRESUMEN
Copper (Cu) is a co-factor for several essential metabolic enzymes. Disruption of Cu homeostasis results in genetic diseases such as Wilson's disease. Here, we show that the zinc transporter 1 (ZnT1), known to export zinc (Zn) out of the cell, also mediates Cu2+ entry into cells and is required for Cu2+-induced cell death, cuproptosis. Structural analysis and functional characterization indicate that Cu2+ and Zn2+ share the same primary binding site, allowing Zn2+ to compete for Cu2+ uptake. Among ZnT members, ZnT1 harbors a unique inter-subunit disulfide bond that stabilizes the outward-open conformations of both protomers to facilitate efficient Cu2+ transport. Specific knockout of the ZnT1 gene in the intestinal epithelium caused the loss of Lgr5+ stem cells due to Cu deficiency. ZnT1, therefore, functions as a dual Zn2+ and Cu2+ transporter and potentially serves as a target for using Zn2+ in the treatment of Wilson's disease caused by Cu overload.
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Proteínas de Transporte de Catión , Cobre , Zinc , Animales , Humanos , Ratones , Transporte Biológico , Proteínas de Transporte de Catión/metabolismo , Proteínas de Transporte de Catión/genética , Cobre/metabolismo , Células HEK293 , Degeneración Hepatolenticular/metabolismo , Degeneración Hepatolenticular/genética , Mucosa Intestinal/metabolismo , Zinc/metabolismoRESUMEN
High-affinity potassium transporters (HKTs) are well known proteins that govern the partitioning of Na+ between roots and shoots. Six HvHKTs were identified in barley and designated as HvHKT1.1, HvHKT1.3, HvHKT1.4, HvHKT1.5, HvHKT2.1 and HvHKT2.2 according to their similarity to previously reported OsHKTs. Among these HvHKTs, HvHKT1.4 was highly up-regulated under salinity stress in both leaves and roots of Golden Promise. Subcellular localization analysis showed that HvHKT1.4 is a plasma-membrane-localized protein. The knockout mutants of HvHKT1.4 showed greater salinity sensitivity and higher Na+ concentration in leaves than wild-type plants. Haplotype analysis of HvHKT1.4 in 344 barley accessions showed 15 single nucleotide substitutions in the CDS region, belonging to five haplotypes. Significant differences in mean salinity damage scores, leaf Na+ contents and Na+/K+ were found between Hap5 and other haplotypes with Hap5 showing better salinity tolerance. The results indicated that HvHKT1.4 can be an effective target in improving salinity tolerance through ion homeostasis.
Asunto(s)
Hordeum , Proteínas de Plantas , Tolerancia a la Sal , Hordeum/genética , Hordeum/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Tolerancia a la Sal/genética , Sodio/metabolismo , Potasio/metabolismo , Proteínas de Transporte de Catión/genética , Proteínas de Transporte de Catión/metabolismo , Regulación de la Expresión Génica de las Plantas , Haplotipos , Hojas de la Planta/metabolismo , Hojas de la Planta/genética , Raíces de Plantas/metabolismo , Raíces de Plantas/genética , SalinidadRESUMEN
Long non-coding RNAs play a key role in silicosis, a fatal fibrotic lung disease, and there is an urgent need to develop new treatment targets. Long intergenic non-protein-coding RNA 3047 (LINC03047) is associated with cancer, but its role and mechanism in the progression of silicosis require further elucidation. This study investigated the function of LINC03047 in the epithelial-mesenchymal transition (EMT) during silicosis progression. LINC03047 expression was upregulated in SiO2-treated BEAS-2B and A549 cells, promoting SiO2-induced ferroptosis and subsequent EMT. Moreover, knockdown of LINC03047 significantly decreased the expression of solute carrier family 39 member 14 (SLC39A14), a ferrous iron transporter, and inhibition of SLC39A14 alleviated the ferroptosis and EMT caused by LINC03047 overexpression. We further investigated that NF-κB p65 (RELA) was critical for LINC03047 transcription in SiO2-treated BEAS-2B and A549 cells. In vivo experiments showed that SLC39A14 deficiency improved SiO2-induced lipid peroxidation and EMT. Collectively, our study reveals the function of the RELA/LINC03047/SLC39A14 axis in SiO2-induced ferroptosis and EMT, thereby contributing to the identification of novel drug targets for silicosis therapy.
Asunto(s)
Proteínas de Transporte de Catión , Transición Epitelial-Mesenquimal , Ferroptosis , ARN Largo no Codificante , Dióxido de Silicio , Silicosis , Factor de Transcripción ReIA , Ferroptosis/genética , Humanos , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Proteínas de Transporte de Catión/genética , Proteínas de Transporte de Catión/metabolismo , Dióxido de Silicio/toxicidad , Animales , Transición Epitelial-Mesenquimal/genética , Células A549 , Silicosis/patología , Silicosis/metabolismo , Silicosis/genética , Ratones , Factor de Transcripción ReIA/genética , Factor de Transcripción ReIA/metabolismo , Fibrosis Pulmonar/genética , Fibrosis Pulmonar/metabolismo , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/patología , Regulación hacia Arriba , Regulación de la Expresión GénicaRESUMEN
Ammonium transporters (AMTs) are vital plasma membrane proteins facilitating NH4+ uptake and transport, crucial for plant growth. The identification of favorable AMT genes is the main goal of improving ammonium-tolerant algas. However, there have been no reports on the systematic identification and expression analysis of Chlamydomonas reinhardtii (C. reinhardtii) AMT genes. This study comprehensively identified eight CrAMT genes, distributed across eight chromosomes, all containing more than 10 transmembrane structures. Phylogenetic analysis revealed that all CrAMTs belonged to the AMT1 subfamily. The conserved motifs and domains of CrAMTs were similar to those of the AMT1 members of OsAMTs and AtAMTs. Notably, the gene fragments of CrAMTs are longer and contain more introns compared to those of AtAMTs and OsAMTs. And the promoter regions of CrAMTs are enriched with cis-elements associated with plant hormones and light response. Under NH4+ treatment, CrAMT1;1 and CrAMT1;3 were significantly upregulated, while CrAMT1;2, CrAMT1;4, and CrAMT1;6 saw a notable decrease. CrAMT1;7 and CrAMT1;8 also experienced a decline, albeit less pronounced. Transgenic algas with overexpressed CrAMT1;7 did not show a significant difference in growth compared to CC-125, while transgenic algas with CrAMT1;7 knockdown exhibited growth inhibition. Transgenic algas with overexpressed or knocked-down CrAMT1;8 displayed reduced growth compared to CC-125, which also resulted in the suppression of other CrAMT genes. None of the transgenic algas showed better growth than CC-125 at high ammonium levels. In summary, our study has unveiled the potential role of CrAMT genes in high-ammonium environments and can serve as a foundational research platform for investigating ammonium-tolerant algal species.