RESUMO

The MnSOD Ala16Val single nucleotide polymorphism (SNP) has shown to be associated to risk factors of several metabolic and vascular diseases. However, little is known about interaction between MnSOD Ala16Val SNP in stroke, a frequent neurologic disease that involves clinic manifestations such as motor deficits and spasticity. In this sense, we decided to investigate the relationship between MnSOD Ala16Val SNP with spasticity in stroke and also its influence on interleukin levels, BDNF, and glycolipid parameters. Eighty post-stroke subjects and 80 healthy controls were investigated. We showed a higher spasticity, levels of total cholesterol, LDL, IL-1ß, IL-6, and INF-γ in VV post-stroke group. Interesting, we found a correlation between IL-1ß levels and spasticity in VV post-stroke. Triglycerides, glucose levels and caspases (1 and 3) activation were significantly higher, as well as BDNF levels were lower in VV and AV post-stroke. DNA damage was higher in post-stroke group. Thus, we can suggest that the V allele has a worse glycolipid profile, which would facilitate changes in neurovascular homeostasis. These events associated with an increase in inflammatory markers and a reduction in BDNF can contribute with the stroke and a worse clinical evolution in relation to spasticity in patients with VV genotype.

Assuntos

Interleucina-6 , Acidente Vascular Cerebral , Fator Neurotrófico Derivado do Encéfalo/genética , Caspases/genética , LDL-Colesterol/genética , Genótipo , Glucose , Glicolipídeos , Humanos , Interleucina-1beta/genética , Interleucina-6/genética , Espasticidade Muscular/genética , Polimorfismo de Nucleotídeo Único , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/genética , Superóxido Dismutase/genética , Triglicerídeos

RESUMO

Some of the more than 200 known HPV types are essential for cervical cancer development, the third type of cancer most incident in the female population. However, for the malignant transformation occur, some cofactors are needed, as the reactive oxygen species (ROS), which can be neutralized by the antioxidant system. The SOD2 enzyme, encoded by the same name gene, is found in mitochondria and is part of the first line of defense against oxidative stress damage. Genetic polymorphisms can act by altering the efficiency of the enzyme, among which the most studied is the rs4880. Thus, the purpose of the present study was to evaluate the association of this polymorphism with HPV infection and the development of low and high grade squamous intraepithelial lesions (LSIL and HSIL) and cervical cancer, in 407 women attended by the public health system in Brazil. HPV detection in cervical secretion samples was carried out by polymerase chain reaction (PCR) and blood samples were used for polymorphism genotyping through PCR followed by restriction fragment length polymorphism (RFLP). PCR and restriction products were subjected to 10% polyacrylamide gel electrophoresis. HPV negative group (control) included 158 women and the HPV positive group (case) 249 women. The infected group was divided into No Lesion (n = 90), LSIL (n = 20), HSIL (n = 67) and cervical cancer (n = 72). The data found on socio-epidemiological characteristics and habits corroborated with data found in the literature. The distribution of genotypes in the control group was 51.9% women TC, 29.8% TT and 18.3% CC. In the case group, the distribution was 55.0% women TC, 26.1% TT and 18.9% CC. This is the first study evaluating the influence of SOD2 rs4880 polymorphism on HPV infection, the development of cervical intraepithelial lesions and cervical cancer in a Brazilian population, although additional studies are needed to corroborate the results.

Assuntos

Biomarcadores Tumorais/genética , Polimorfismo de Nucleotídeo Único , Lesões Intraepiteliais Escamosas/genética , Superóxido Dismutase/genética , Displasia do Colo do Útero/genética , Neoplasias do Colo do Útero/genética , Adulto , Brasil , Estudos Transversais , Feminino , Frequência do Gene , Predisposição Genética para Doença , Humanos , Pessoa de Meia-Idade , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/virologia , Fenótipo , Medição de Risco , Fatores de Risco , Lesões Intraepiteliais Escamosas/enzimologia , Lesões Intraepiteliais Escamosas/patologia , Lesões Intraepiteliais Escamosas/virologia , Neoplasias do Colo do Útero/enzimologia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , Adulto Jovem , Displasia do Colo do Útero/enzimologia , Displasia do Colo do Útero/patologia , Displasia do Colo do Útero/virologia

RESUMO

Shrimp are increasingly exposed to warmer temperatures and lower oxygen concentrations in their habitat due to climate change. These conditions may lead to oxidative stress and apoptosis. We studied the effects of high temperature, hypoxia, reoxygenation, and the combination of these factors on lipid peroxidation, protein carbonylation, and caspase-3 activity in gills of white shrimp Litopenaeus vannamei. Silencing of mitochondrial manganese superoxide dismutase (mMnSOD) was used to determine the role of this enzyme in response to the abiotic stressors described above, to avoid oxidative damage and apoptosis. In addition, mMnSOD gene expression and mitochondrial SOD activity were evaluated to determine the efficiency of silencing this enzyme. The results showed that there was no effect of the abiotic stress conditions on the thiobarbituric acid reactive substances (TBARS), but protein carbonylation increased in all the oxidative stress treatments and caspase-3 activity decreased in hypoxia at 28 °C. On the other hand, mMnSOD-silenced shrimp experienced higher oxidative stress, since TBARS, carbonylated proteins and caspase-3 activity increased in some silenced treatments. Unexpectedly, mitochondrial SOD activity increased in some of the silenced treatments as well. Altogether, these results suggest that mMnSOD has a key role in shrimp for the prevention of oxidative damage development and induction of apoptosis in response to hypoxia, reoxygenation, high temperature, and their interactions, as conditions derived from climate change.

Assuntos

Caspase 3/metabolismo , Crustáceos/fisiologia , Técnicas de Silenciamento de Genes , Temperatura Alta , Hipóxia/metabolismo , Mitocôndrias/enzimologia , Estresse Oxidativo/genética , Oxigênio/metabolismo , Superóxido Dismutase/genética , Animais , Crustáceos/metabolismo , Inativação Gênica , Superóxido Dismutase/metabolismo

RESUMO

OBJECTIVE: The objective of the study was to evaluate the neurocognitive profile and its relation with Ala16ValMnSOD polymorphism in epilepsy and if these clinical parameters are linked to oxidative stress and inflammatory markers. METHODS: Patients with epilepsy (n = 31) and healthy subjects (n = 42) were recruited. A neuropsychological evaluation was performed in both groups through a battery of cognitive tests. Oxidative stress, inflammatory markers, apoptotic factors, and deoxyribonucleic acid (DNA) damage were measured in blood samples. RESULTS: Statistical analyses showed the association of MnSOD Ala16Val polymorphism with cognitive impairment, including praxis, perception, attention, language, executive functions, long-term semantic memory, short-term visual memory, and total memory in patients with epilepsy and Valine-Valine (VV) genotype compared with the control group. Compared with the controls and patients with epilepsy, Alanine-Alanine (AA), and Alanine-Valine (AV) genotype, the patients with epilepsy and VV genotype exhibited higher levels of tumor necrosis factor alpha (TNF-α), interleukin 1ß (IL-1ß), interleukin 6 (IL-6), activation of caspases 1 and 3 (CASP-1 and -3), and DNA damage. Our findings also showed higher carbonyl protein and thiobarbituric acid reactive substances (TBARS) levels as well as an increased superoxide dismutase (SOD) and acetylcholinesterase (AChE) activities in patients with epilepsy and VV genotype. CONCLUSION: This study supports the evidence of a distinct neuropsychological profile in patients with epilepsy, especially those with the VV genotype. Furthermore, our results suggest that oxidative and inflammatory pathways may be associated with genetic polymorphism and cognitive dysfunction in patients with epilepsy.

Assuntos

Disfunção Cognitiva , Epilepsia , Disfunção Cognitiva/complicações , Disfunção Cognitiva/genética , Epilepsia/complicações , Epilepsia/genética , Genótipo , Humanos , Estresse Oxidativo/genética , Polimorfismo Genético , Superóxido Dismutase/genética

RESUMO

Studies suggest that redox imbalance may be closely associated with pathological aging, contributing effectively to the genesis of several chronic diseases. One of the major defence enzymes against oxidation is Manganese-dependent superoxide dismutase (MnSOD) that acts within the mitochondria. The gene encoding this enzyme is polymorphic and Val16Ala variant is one of its most investigated polymorphisms regarding aging and oxidative stress. This study aimed to verify the occurrence of the MnSOD Val16Ala gene polymorphism association with markers of REDOX metabolism in the elderly of primary health care. A cross-sectional study was performed. The sample consisted of 270 elderly individuals from Family Health Strategy in the city of Porto Alegre, Rio Grande do Sul, Brazil (EMISUS). The following variables were investigated in all subjects: sociodemographic: gender, age, marital status, schooling and income; Anthropometric: weight, height, body mass index (BMI); REDOX markers: advanced oxidation protein products (AOPP), ischemia-modified albumin (IMA), nitric oxide metabolites (NOx), ferric reducing ability of plasma (FRAP) and malondialdehyde (MDA), MnSOD Val16Ala gene polymorphism. Val16Ala gene polymorphism was evaluated by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). Statistically significant associations were observed in the elderly with AA genotype compared to those with VV genotype, concerning AOPP (p = 0.023) and FRAP (p = 0.027) quartile frequencies, respectively. No statistically significant differences were observed between MnSOD genotypes with MDA, NOx and IMA oxidative markers. Val16Ala gene polymorphism is associated with AOPP and FRAP quartiles frequencies in the elderly of primary health care.

Assuntos

Polimorfismo Genético/genética , Atenção Primária à Saúde , Superóxido Dismutase/genética , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/metabolismo , Brasil , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oxirredução , Superóxido Dismutase/metabolismo

RESUMO

Climate warming has been increasing ocean water temperature and decreasing oxygen concentrations, exposing aquatic organisms to environmental stress conditions. The shrimp Litopenaeus vannamei manages to survive these harsh environmental conditions by enhancing their antioxidant defenses, among other strategies. In this study, we report the mitochondrial manganese superoxide dismutase (mMnSOD) nucleotide and deduced amino acid sequences and its gene expression in L. vannamei tissues. The deduced protein has 220 amino acids with a signal peptide of 20 amino acids. Expression of mMnSOD was analyzed in hepatopancreas, gills and muscle, where gills had highest expression in normoxic conditions. In addition, shrimp were subjected to high temperature, hypoxia and reoxygenation to analyze the effect on the expression of mMnSOD and SOD activity in mitochondria. High temperature and hypoxia showed a synergistic effect in the up-regulation on expression of mMnSOD in gills and hepatopancreas. Moreover, induction in SOD activity was found in the mitochondrial fraction from gills of normoxia at high temperature, probably due to an overproduction of reactive oxygen species caused by an elevated metabolic rate due to the stress temperature. These results suggest that the combined stress conditions of hypoxia and high temperature trigger molecularly the antioxidant response in L. vannamei in a higher degree than only one stressor.

Assuntos

Proteínas de Artrópodes , Mitocôndrias/metabolismo , Oxigênio , Penaeidae , Superóxido Dismutase , Temperatura , Sequência de Aminoácidos , Animais , Proteínas de Artrópodes/genética , Proteínas de Artrópodes/metabolismo , Sequência de Bases , Penaeidae/genética , Penaeidae/metabolismo , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo

RESUMO

The MnSOD Ala16Val single nucleotide polymorphism (SNP) has shown to be associated to inflammatory pathways and many metabolic disorders, such as obesity and dyslipidemia. Metabolic syndrome (MetS) is an emergent problem among patients with epilepsy. However, little is known about interaction between MnSOD Ala16Val SNP and metabolic comorbities in epilepsy. Thus, we investigated the relationship between MnSOD Ala16Val SNP with epilepsy and its influence on MetS, inflammation, apoptosis and DNA damage parameters. Ninety subjects were evaluated (47 epilepsy patients and 43 healthy controls) by questionnaires and laboratorial exams. Levels of inflammatory, apoptotic and DNA damage markers, as well as MnSOD polymorphism were assessed. An increased proportion of VV genotype in epilepsy group when compared to control group was observed. Tumor Necrosis Factor-α (TNF-α), Acetylcholinesterase, caspase-8, and Picogreen levels were increased in VV epilepsy group. An important correlation between TNF-α vs caspase-8, and Cholesterol vs. Triglycerides was observed in the epilepsy group with VV genotype. Our findings suggest that the MnSOD Ala16Val SNP might have an important role in epilepsy, mainly in patients with generalized seizures and particularly with VV genotype. The metabolic parameters also presented significant results in epilepsy group with VV genotype, which applying attention in view of further consequences and disorders that could be developed.

Assuntos

Substituição de Aminoácidos , Colesterol/metabolismo , Convulsões/genética , Superóxido Dismutase/genética , Triglicerídeos/metabolismo , Acetilcolinesterase/genética , Adulto , Estudos de Casos e Controles , Caspase 8/genética , Dano ao DNA , Feminino , Proteínas Ligadas por GPI/genética , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Estresse Oxidativo , Fator de Necrose Tumoral alfa/genética

RESUMO

Micronutrients are indispensable for adequate metabolism, such as biochemical function and cell production. The production of blood cells is named haematopoiesis and this process is highly consuming due to the rapid turnover of the haematopoietic system and consequent demand for nutrients. It is well established that micronutrients are relevant to blood cell production, although some of the mechanisms of how micronutrients modulate haematopoiesis remain unknown. The aim of the present review is to summarise the effect of Fe, Mn, Ca, Mg, Na, K, Co, iodine, P, Se, Cu, Li and Zn on haematopoiesis. This review deals specifically with the physiological requirements of selected micronutrients to haematopoiesis, showing various studies related to the physiological requirements, deficiency or excess of these minerals on haematopoiesis. The literature selected includes studies in animal models and human subjects. In circumstances where these minerals have not been studied for a given condition, no information was used. All the selected minerals have an important role in haematopoiesis by influencing the quality and quantity of blood cell production. In addition, it is highly recommended that the established nutrition recommendations for these minerals be followed, because cases of excess or deficient mineral intake can affect the haematopoiesis process.

Assuntos

Células Sanguíneas/metabolismo , Hematopoese/efeitos dos fármacos , Minerais/farmacologia , Necessidades Nutricionais , Oligoelementos/farmacologia , Animais , Deficiências Nutricionais/complicações , Humanos , Estado Nutricional

RESUMO

The SOD2 polymorphism Val16Ala T→C influences the antioxidative response. This study investigated the association of the SOD2 polymorphism and superoxide dismutase (SOD) activity with the vaso-occlusive crisis (VOC) and acute splenic sequestration (ASS) in children with sickle cell anemia (SCA). One hundred ninety-five children with SCA aged 1-9 years old were analyzed. The TC and CC genotypes were associated with lower SOD activity compared with the TT genotype (p=0.0321; p=0.0253, respectively). Furthermore, TC and CC were more frequent in patients with VOC or ASS (p=0.0285; p=0.0090, respectively). These results suggest that the SOD2 polymorphism associated with low SOD activity could be a susceptibility factor for the occurrence of VOC and ASS.

RESUMO

Superoxide-hydrogen peroxide (S-HP) imbalance genetically caused by a gene polymorphism in the human manganese superoxide dismutase enzyme (Val16Ala-MnSOD) is associated with several diseases. Into mitochondria, MnSOD catalyses superoxide radical producing HP and oxygen. Ala-MnSOD genotype presents a high MnSOD efficiency and generates the highest HP concentrations that has been associated with the risk of several cancer types. Cellular selenoenzymes glutathione peroxidase and thioredoxin reductase (TrxR) and catalase (CAT) are essential to HP removal produced in excess in cells. Since, synthesis and activities of selenoenzymes are selenium dependent, we hypothesized that AA-MnSOD cells could have an improvement on antioxidant status undergoing Seleno-L-methionine (SeMet) treatment. This study performed an in vitro protocol to evaluate the response of peripheral blood mononuclear cells (PBMC) carriers of different Val16Ala-MnSOD genotypes exposed to SeMet. SeMet effects on cell viability, apoptosis induction and modulation of oxidative variables were determined using spectrophotometric, flow cytometry, fluorimetric and immunoassays. Gene modulation of antioxidant enzymes was also performed by qRT-PCR. From an initial protocol using heterozygous (AV) cells was determined that 1nM SeMet presented a cytoprotective effect. However, whereas this concentration did not change AA viability, in VV cells it was cytotoxic by increasing necrosis events. SeMet induced higher selenoenzymes levels in AA and VV cells and decreased oxidative markers levels including DNA damage. The results suggest a pharmacogenetic positive response of SeMet effect on AA-cells. Future studies in vivo could be essential to evaluate the potential clinical impact of S-HP imbalance after use of foods or supplements containing SeMet.

Assuntos

Peróxido de Hidrogênio/metabolismo , Leucócitos Mononucleares/efeitos dos fármacos , Polimorfismo Genético , Selenometionina/farmacologia , Superóxido Dismutase/genética , Superóxidos/metabolismo , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Humanos , Leucócitos Mononucleares/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Selenometionina/administração & dosagem , Relação Estrutura-Atividade , Superóxido Dismutase/metabolismo

RESUMO

Stroke risk has been associated to the progression of carotid plaques due to high glucose levels and lipid accumulation, which are greatly associated to cerebral injury, brain oxidative stress, and apoptosis. The ALA16VAL-MnSOD gene single nucleotide polymorphism (SNP) has shown to modulate risk factors of several metabolic and vascular diseases, such as blood glucose (GLU) and lipid levels. However, the association of these factors in stroke patients has not been studied to date. Thus, we evaluated the influence of the Ala16Val-MnSOD SNP on lipid profile, GLU levels, oxidative and DNA damage of 44 patients in a late phase of stroke (>6months). The statistical analysis showed a greater proportion of VV carries in stroke patients. The results also indicated that stroke patients had higher cholesterol (CHO) and GLU levels when compared to healthy counterparts. Interestingly, V allele carriers with stroke showed higher levels of CHO and GLU when compared to AA stroke and healthy counterparts. Our findings suggest that oxidative stress markers are still increased even after 6 months of cerebral injury. Furthermore, we propose that the Ala16Val-MnSOD SNPs may contribute to hypercholesterolemia and higher GLU levels, increasing the risk to neurovascular events that may lead to stroke.

Assuntos

Predisposição Genética para Doença , Glucose/metabolismo , Hipercolesterolemia/genética , Polimorfismo de Nucleotídeo Único , Acidente Vascular Cerebral/genética , Superóxido Dismutase/genética , Substituição de Aminoácidos , Estudos de Casos e Controles , Humanos

RESUMO

As superoxide is a key molecule of inflammatory activation, superoxide-hydrogen peroxide (S-HP) imbalance genetically caused could alter immunosenescence patterns. To test this hypothesis, we collected and cultured peripheral blood mononuclear cells (PBMCs) carrier's different genotypes of a genetic polymorphism located in the superoxide dismutase manganese-dependent gene (Val16Ala-SOD2). We used an in vitro genetic model based on previous studies, which suggested an association between homozygous genotypes (AA and VV) and alterations in oxidative-inflammatory mediators. PBMCs collected from young healthy volunteers were cultured in the presence of phytohemagglutinin, as well as the following cell culture passages obtained from the 72-hour initial culture. Each follow passage started with the same cell concentration (1 × 105 cells). The general immunosenescence pattern was observed independent of SOD2 genotypes: cellular proliferation until the 15th passage, when cellular arrestment occurred in the G0/G1 phase. From the 10th passage, a higher proliferative state was observed, indicating inflammatory hyperactivation, with an increase in the levels of inflammatory cytokines (IL-1, IL-6, and TNFα), nitric oxide, superoxide, lipoperoxidation, protein carbonylation, reactive oxygen species, and DNA damage. The S-HP imbalance affected the intensity of some immunosenescence parameters. AA cells, which present basal high HP levels, were associated with higher DNA damage and lipoperoxidation levels, whereas VV, which present basal high S levels, was associated with higher proinflammatory cytokine levels. In summary, the results suggested that a basal S-HP imbalance could affect the intensity of some immunosenescence markers, and this influence could explain the potential association between an imbalance of genotypes (AA and VV) and the risk of developing some chronic diseases.

Assuntos

Peróxido de Hidrogênio/metabolismo , Imunossenescência , Superóxidos/metabolismo , Adulto , Apoptose , Biomarcadores/metabolismo , Células Cultivadas , Citometria de Fluxo , Humanos , Estresse Oxidativo

RESUMO

Application of yeast is increasing to improve welfare and promotes growth in aquaculture. The halotolerant yeast Debaryomyces hansenii is normally a non-pathogenic yeast with probiotic properties and potential source of antioxidant enzymes as superoxide dismutase. Here, first, we characterized the sequence features of MnSOD and icCu/ZnSOD from Pacific red snapper, and second, we evaluated the potential antioxidant immune responses of the marine yeast Debaryomyces hansenii strain CBS004 in leukocytes which were then subjected to Vibrio parahaemolyticus infection. In silico analysis revealed that LpMnSOD consisted of 1186 bp, with an ORF of 678 bp encoding a 225 amino acid protein and LpicCu/ZnSOD consisted of 1090 bp in length with an ORF of 465 bp encoding a 154 amino acid protein. Multiple alignment analyzes revealed many conserved regions and active sites among its orthologs. In vitro assays using head-kidney and spleen leukocytes immunostimulated with D. hansenii and zymosan in response to V. parahaemolyticus infection reveled that D. hansenii strain CBS004 significantly increased transcriptions of MnSOD and icCu/ZnSOD genes. Flow cytometry assay showed that D. hansenii was able to inhibit apoptosis caused by V. parahaemolyticus in the Pacific red snapper leukocytes and enhanced the phagocytic capacity in head-kidney leukocytes. Immunological assays reveled an increased in superoxide dismutase and peroxidase activities, as well as, in nitric oxide production and reactive oxygen species production (respiratory burst) in fish stimulated with D. hansenii. Finally, our results. These results strongly support the idea that marine yeast Debaryomyces hansenii strain CBS004 can stimulate the antioxidant immune mechanism in head-kidney and spleen leukocytes.

Assuntos

Debaryomyces/imunologia , Doenças dos Peixes/imunologia , Proteínas de Peixes/metabolismo , Leucócitos/imunologia , Perciformes/imunologia , Superóxido Dismutase/metabolismo , Vibrioses/imunologia , Vibrio parahaemolyticus/imunologia , Sequência de Aminoácidos , Animais , Apoptose , Clonagem Molecular , Doenças dos Peixes/microbiologia , Proteínas de Peixes/genética , Imunidade Inata , Estresse Oxidativo , Fagocitose , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/genética , Regulação para Cima , Vibrioses/microbiologia

RESUMO

INTRODUCTION: Several studies have reported increased oxidation of lipids, proteins and DNA in the brains of patients with Alzheimer disease (AD). Moreover, these patients display differences in the activity and polymorphisms of the genes encoding the enzymes GST (T1, M1) and MnSOD. For these reasons, we designed a study of the variability in GSTT1, GSTM1, and MnSOD genes in healthy and AD groups from a Venezuelan population. METHODS: We included 179 unrelated Venezuelan subjects classified as either AD patients (n=79) or healthy individuals (n=100). Presence or absence of the GSTT1/GSTM1 genes was determined using PCR-SSP, and polymorphisms of MnSOD and APOE genes were identified with PCR-RFLP. RESULTS: The genotype GSTT1+/GSTM1- seems to favour development of AD (OR=2.06, P=.01). The risk level is higher when it is combined with the ɛ4 allele of the APOE gene: GSTT1+/GSTM1-/ɛ3ɛ4 (OR=3.07, P=.05), GSTT1+/GSTM1-/ɛ4ɛ4 (OR=5.52, P=.02). The Ala-9Val polymorphism does not appear to be related to AD. However, the presence of the Ala/Ala genotype increases the risk provided by the ɛ4 allele of the APOE gene: AlaAla/ɛ3ɛ4 (OR=3.47, P=.03), AlaAla/ɛ4ɛ4 (OR=6.3, P=.01). CONCLUSIONS: The results support the hypothesis that impaired mitochondrial function and increased oxidative damage are involved in the pathogenesis of AD. It is important to study other genes related to oxidative stress and antioxidant pathways which could be involved in susceptibility to AD.

Assuntos

Doença de Alzheimer/genética , Apolipoproteína E4/genética , Glutationa Transferase/genética , Superóxido Dismutase/genética , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Mitocôndrias/genética , Mitocôndrias/metabolismo , Polimorfismo Genético/genética , Venezuela/epidemiologia

RESUMO

Germin-like proteins (GLPs) are encoded by a family of genes found in all plants, and in terms of function, the GLPs are implicated in the response of plants to biotic and abiotic stresses. CchGLP is a gene encoding a GLP identified in a geminivirus-resistant Capsicum chinense Jacq accession named BG-3821, and it is important in geminivirus resistance when transferred to susceptible tobacco in transgenic experiments. To characterize the role of this GLP in geminivirus resistance in the original accession from which this gene was identified, this work aimed at demonstrating the possible role of CchGLP in resistance to geminiviruses in Capsicum chinense Jacq. BG-3821. Virus-induced gene silencing studies using a geminiviral vector based in PHYVV component A, displaying that silencing of CchGLP in accession BG-3821, increased susceptibility to geminivirus single and mixed infections. These results suggested that CchGLP is an important factor for geminivirus resistance in C. chinense BG-3821 accession.

Assuntos

Capsicum/imunologia , Capsicum/virologia , Resistência à Doença , Geminiviridae/crescimento & desenvolvimento , Geminiviridae/imunologia , Proteínas de Plantas/metabolismo , Capsicum/genética , Coinfecção/imunologia , Coinfecção/virologia , Inativação Gênica , Doenças das Plantas/genética , Doenças das Plantas/imunologia , Doenças das Plantas/virologia , Proteínas de Plantas/genética

RESUMO

With devastating increase in population there is a great necessity to increase crop productivity of staple crops but the productivity is greatly affected by various abiotic stress factors such as drought, salinity. An attempt has been made a brief account on abiotic stress resistance of major cereal crops viz. In spite of good successes obtained on physiological and use molecular biology, the benefits of this high cost technology are beyond the reach of developing countries. This review discusses several morphological, anatomical, physiological, biochemical and molecular mechanisms of major cereal crops related to the adaptation of these crop to abiotic stress factors. It discusses the effect of abiotic stresses on physiological processes such as flowering, grain filling and maturation and plant metabolisms viz. photosynthesis, enzyme activity, mineral nutrition, and respiration. Though significant progress has been attained on the physiological, biochemical basis of resistance to abiotic stress factors, very little progress has been achieved to increase productivity under sustainable agriculture. Therefore, there is a great necessity of inter-disciplinary research to address this issue and to evolve efficient technology and its transfer to the farmers' fields.

Assuntos

Grão Comestível/fisiologia , Adaptação Fisiológica , Brassinosteroides , Produtos Agrícolas , Grão Comestível/classificação , Espécies Reativas de Oxigênio/metabolismo

RESUMO

The chemotherapeutic isothiocyanate sulforaphane (SFN) was early linked to anticarcinogenic and antiproliferative activities. Soon after, this compound, derived from cruciferous vegetables, became an excellent and useful trial for anti-cancer research in experimental models including growth tumor, metastasis, and angiogenesis. Many subsequent reports showed modifications in mitochondrial signaling, functionality, and integrity induced by SFN. When cytoprotective effects were found in toxic and ischemic insult models, seemingly contradictory behaviors of SFN were discovered: SFN was inducing deleterious changes in cancer cell mitochondria that eventually would carry the cell to death via apoptosis and also was protecting noncancer cell mitochondria against oxidative challenge, which prevented cell death. In both cases, SFN exhibited effects on mitochondrial redox balance and phase II enzyme expression, mitochondrial membrane potential, expression of the family of B cell lymphoma 2 homologs, regulation of proapoptotic proteins released from mitochondria, activation/inactivation of caspases, mitochondrial respiratory complex activities, oxygen consumption and bioenergetics, mitochondrial permeability transition pore opening, and modulation of some kinase pathways. With the ultimate findings related to the induction of mitochondrial biogenesis by SFN, it could be considered that SFN has effects on mitochondrial dynamics that explain some divergent points. In this review, we list the reports involving effects on mitochondrial modulation by SFN in anti-cancer models as well as in cytoprotective models against oxidative damage. We also attempt to integrate the data into a mechanism explaining the various effects of SFN on mitochondrial function in only one concept, taking into account mitochondrial biogenesis and dynamics and making a comparison with the theory of reactive oxygen species threshold of cell death. Our interest is to achieve a complete view of cancer and protective therapies based on SFN that can be extended to other chemotherapeutic compounds with similar characteristics. The work needed to test this hypothesis is quite extensive.

Assuntos

Antioxidantes/farmacologia , Isotiocianatos/farmacologia , Mitocôndrias/fisiologia , Animais , Apoptose , Humanos , Mitocôndrias/efeitos dos fármacos , Renovação Mitocondrial/efeitos dos fármacos , Neoplasias/metabolismo , Estresse Oxidativo , Sulfóxidos

RESUMO

Reactive oxygen and nitrogen species regulate a wide array of signaling pathways that governs cardiovascular physiology. However, oxidant stress resulting from disrupted redox signaling has an adverse impact on the pathogenesis and progression of cardiovascular diseases. In this review, we address how redox signaling and oxidant stress affect the pathophysiology of cardiovascular diseases such as ischemia-reperfusion injury, hypertension and heart failure. We also summarize the benefits of exercise training in tackling the hyperactivation of cellular oxidases and mitochondrial dysfunction seen in cardiovascular diseases.

Assuntos

Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/fisiopatologia , Exercício Físico , Estresse Oxidativo , Transdução de Sinais , Antioxidantes/metabolismo , Exercício Físico/fisiologia , Humanos , Mitocôndrias/metabolismo , Oxirredução , Espécies Reativas de Oxigênio/metabolismo

RESUMO

The aim of this study was to analyze the effects of chronic oxidative stress on mitochondrial function and its relationship to progressive neurodegeneration in the hippocampus of rats chronically exposed to ozone. Animals were exposed to 0.25 ppm ozone for 7, 15, 30, or 60 days. Each group was tested for (1) protein oxidation and, manganese superoxide dismutase (Mn-SOD), glutathione peroxidase (GPx) and succinate dehydrogenase (SDH) activity using spectrophotometric techniques, (2) oxygen consumption, (3) cytochrome c, inducible nitric oxide synthase (iNOS), peroxisome proliferator-activated receptor γ Co-activator 1α (PGC-1α), B-cell lymphoma (Bcl-2), and Bax expression using Western blotting, (4) histology using hematoxylin and eosin staining, and (5) mitochondrial structure using electron microscopy. Our results showed increased levels of carbonyl protein and Mn-SOD activity after 30 days of ozone exposure and decreased GPx activity. The SDH activity decreased from 7 to 60 days of exposure. The oxygen consumption decreased at 60 days. Western blotting showed an increase in cytochrome c at 60 days of ozone exposure and an increase in iNOS up to 60 days of ozone exposure. The expression of PGC-1α was decreased after 15, 30, and 60 days compared to the earlier time Bcl-2 was increased at 60 days compared to earlier time points, and Bax was increased after 30 and 60 days of exposure compared to earlier time points. We observed cellular damage, and mitochondrial swelling with a loss of mitochondrial cristae after 60 days of exposure. These changes suggest that low doses of ozone caused mitochondrial abnormalities that may lead to cell damage.

Assuntos

Hipocampo/metabolismo , Hipocampo/patologia , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Estresse Oxidativo/fisiologia , Animais , Western Blotting , Imuno-Histoquímica , Oxidantes Fotoquímicos/toxicidade , Ozônio/toxicidade , Ratos , Ratos Wistar

RESUMO

The aim of the present review is to offer a current perspective about the consequences of hypoglycemia and its impact on the diabetic disorder due to the increasing incidence of diabetes around the world. The main consequence of insulin treatment in type 1 diabetic patients is the occurrence of repetitive periods of hypoglycemia and even episodes of severe hypoglycemia leading to coma. In the latter, selective neuronal death is observed in brain vulnerable regions both in humans and animal models, such as the cortex and the hippocampus. Cognitive damage subsequent to hypoglycemic coma has been associated with neuronal death in the hippocampus. The mechanisms implicated in selective damage are not completely understood but many factors have been identified including excitotoxicity, oxidative stress, zinc release, PARP-1 activation and mitochondrial dysfunction. Importantly, the diabetic condition aggravates neuronal damage and cognitive failure induced by hypoglycemia. In the absence of coma prolonged and severe hypoglycemia leads to increased oxidative stress and discrete neuronal death mainly in the cerebral cortex. The mechanisms responsible for cell damage in this condition are still unknown. Recurrent moderate hypoglycemia is far more common in diabetic patients than severe hypoglycemia and currently important efforts are being done in order to elucidate the relationship between cognitive deficits and recurrent hypoglycemia in diabetics. Human studies suggest impaired performance mainly in memory and attention tasks in healthy and diabetic individuals under the hypoglycemic condition. Only scarce neuronal death has been observed under moderate repetitive hypoglycemia but studies suggest that impaired hippocampal synaptic function might be one of the causes of cognitive failure. Recent studies have also implicated altered mitochondrial function and mitochondrial oxidative stress.

Assuntos

Transtornos Cognitivos/complicações , Hipoglicemia/complicações , Neurônios/patologia , Animais , Transtornos Cognitivos/patologia , Humanos , Hipoglicemia/patologia , Hipoglicemia/prevenção & controle