RESUMEN
The aim of this work was to analyse the stability of vertical height reduction genioplasty using biodegradable material, as well as to determine vertical changes of hard and soft tissues during this procedure. Forty patients underwent vertical height reduction genioplasty using two types of biodegradable fixation (Biosorb FX® or OSTEOTRANS-MX®), combined with mandibular setback surgery. We assessed lateral cephalographs over time (pre-operation; immediately post-operation; 3 months, 6 months and 12 months post-operation). We found a mean vertical difference of 0.22mm (standard deviation (SD)=0.49mm) at the menton point immediately post-operation, compared with 12 months post-operation. And there was no statistical significance(P>0.05). The chin hard tissue remained stable from the immediate post-operation period to 1 year post-operation, and the chin soft tissue remained stable from 3 months to 1 year post-operation. The regression equation describing the replacement of hard tissue with soft tissue change, between pre-operation and 12 months post-operation is y=0.590x+0.885 (R2=0.300, P<0.001). We confirm that the use of biodegradable fixation is a stable method, in terms of skeletal tissues, and a relatively stable method, in terms of soft tissues. In vertical height reduction genioplasty, soft tissue does not reflect 100% of the vertical tissue reduction in hard tissues. This data may influence establishment of surgical treatment objectives.
Asunto(s)
Mentoplastia , Procedimientos Quirúrgicos Ortognáticos , Cefalometría , Mentón , Humanos , MandíbulaRESUMEN
Assessing changes in patient's psychological health and oral health-related quality of life (OHRQoL) over time during orthodontic treatment may help clinicians to treat patients more carefully. To evaluate changes in mental health, self-reported masticatory ability and OHRQoL during orthodontic treatment in adults, this prospective study included 66 adults (30 men, 36 women; mean age, 24·2 ± 5·2 years). Each patient completed the Korean versions of the State-Trait Anxiety Inventory, Zung Self-Rating Depression Scale, Rosenberg self-esteem scale, key subjective food intake ability (KFIA) test for five key foods and Oral Health Impact Profile-14 (OHIP-14K) at baseline (T0), 12 months after treatment initiation (T1) and debonding (T2). All variables changed with time. Self-esteem and the total OHIP-14K score significantly decreased and increased, respectively, at T1, with a particular increase in the psychological and social disabilities scores. There were no significant differences in any questionnaire scores before and after treatment. The total OHIP-14K score was positively correlated with trait anxiety and depression, and negatively correlated with self-esteem and KFIA at T0, regardless of the treatment duration. Older patients showed a significant increase in the total OHIP-14K score at T1 and T2. OHRQoL worsened with an increase in the treatment duration. Our results suggest that OHRQoL temporarily deteriorates, with the development of psychological and social disabilities, during orthodontic treatment. This is related to the baseline age, psychological health and self-reported masticatory function. However, patients recover once the treatment is complete.
Asunto(s)
Ingestión de Alimentos/fisiología , Maloclusión/cirugía , Masticación/fisiología , Ortodoncia Correctiva/psicología , Adaptación Psicológica , Adulto , Ingestión de Alimentos/psicología , Femenino , Humanos , Masculino , Maloclusión/psicología , Modelos Psicológicos , Salud Bucal , Aparatos Ortodóncicos Funcionales , Estudios Prospectivos , Calidad de Vida , Autoimagen , Resultado del Tratamiento , Adulto JovenRESUMEN
Reduced food intake ability can restrict an individual's choice of foods and might have a significant impact on the individual's quality of life and mental health. The aim of this study was to evaluate the correlations between self-reported masticatory ability and oral health-related quality of life (OHRQOL) and psychological health. The study included 72 (26 men, 46 women) adults with a mean age of 26·4 ± 8·6 years. Each participant completed the key subjective food intake ability (KFIA) test for five key foods, the Korean version of the Oral Health Impact Profile-14 (OHIP-14K) and three questionnaires for measuring anxiety, depression and self-esteem. The participants were distributed into two groups by sex (a mean age of 23·9 ± 5·2 for men and 27·9 ± 9·8 for women) and by the median KFIA score. There were no significant differences in any of the variables according to sex. Thirty-two participants (12 men, 20 women) in the lower KFIA group had a higher total OHIP-14K (P < 0·001) and depression level (P < 0·05) than the 40 participants (14 men, 26 women) in the higher KFIA group. As the KFIA decreased, OHRQOL worsened (P < 0·001) and depression increased (P < 0·05). Participants with lower KFIA scores were more than 4·3 times as likely as to have a poor OHRQOL than the reference group (odds ratio, 4·348; 95% confidence interval, 1·554-12·170, P < 0·01). Lower subjective food intake ability is associated with a poor oral health-related quality of life and higher depression level.
Asunto(s)
Adaptación Psicológica/fisiología , Ansiedad/psicología , Ingestión de Alimentos/fisiología , Ingestión de Alimentos/psicología , Preferencias Alimentarias/psicología , Masticación/fisiología , Calidad de Vida , Autoinforme , Adolescente , Adulto , Femenino , Alimentos , Humanos , Masculino , Persona de Mediana Edad , Modelos Psicológicos , República de Corea , Autoimagen , Encuestas y Cuestionarios , Adulto JovenRESUMEN
Patients with peripheral nerve injuries, especially severe injury, often face poor nerve regeneration and incomplete functional recovery, even after surgical nerve repair. This review summarizes treatment options of peripheral nerve injuries with current techniques and concepts and reviews developments in research and clinical application of these therapies.
RESUMEN
The periodontal ligament (PDL) functions as an enthesis, a connective tissue attachment that dissipates strains created by mechanical loading. Entheses are mechanoresponsive structures that rapidly adapt to changes in their mechanical loading; here we asked which features of the PDL are sensitive to such in vivo loading. We evaluated the PDL in 4 physiologically relevant mechanical environments, focusing on mitotic activity, cell density, collagen content, osteogenic protein expression, and organization of the tissue. In addition to examining PDLs that supported teeth under masticatory loading and eruptive forces, 2 additional mechanical conditions were created and analyzed: hypoloading and experimental tooth movement. Collectively, these data revealed that the adult PDL is a remarkably quiescent tissue and that only when it is subjected to increased loads--such as those associated with mastication, eruption, and orthodontic tooth movement-does the tissue increase its rate of cell proliferation and collagen production. These data have relevance in clinical scenarios where PDL acclimatization can be exploited to optimize tooth movement.
Asunto(s)
Ligamento Periodontal/fisiología , Animales , Proliferación Celular , Colágeno/metabolismo , Análisis de Elementos Finitos , Inmunohistoquímica , Masticación/fisiología , Ratones , Microscopía Electrónica de Rastreo , Mitosis/fisiología , Estrés Mecánico , Erupción Dental/fisiología , Técnicas de Movimiento DentalRESUMEN
Implants placed with high insertion torque (IT) typically exhibit primary stability, which enables early loading. Whether high IT has a negative impact on peri-implant bone health, however, remains to be determined. The purpose of this study was to ascertain how peri-implant bone responds to strains and stresses created when implants are placed with low and high IT. Titanium micro-implants were inserted into murine femurs with low and high IT using torque values that were scaled to approximate those used to place clinically sized implants. Torque created in peri-implant tissues a distribution and magnitude of strains, which were calculated through finite element modeling. Stiffness tests quantified primary and secondary implant stability. At multiple time points, molecular, cellular, and histomorphometric analyses were performed to quantitatively determine the effect of high and low strains on apoptosis, mineralization, resorption, and collagen matrix deposition in peri-implant bone. Preparation of an osteotomy results in a narrow zone of dead and dying osteocytes in peri-implant bone that is not significantly enlarged in response to implants placed with low IT. Placing implants with high IT more than doubles this zone of dead and dying osteocytes. As a result, peri-implant bone develops micro-fractures, bone resorption is increased, and bone formation is decreased. Using high IT to place an implant creates high interfacial stress and strain that are associated with damage to peri-implant bone and therefore should be avoided to best preserve the viability of this tissue.
Asunto(s)
Implantes Dentales , Fémur/anatomía & histología , Animales , Apoptosis/fisiología , Fenómenos Biomecánicos , Remodelación Ósea/fisiología , Resorción Ósea/fisiopatología , Calcificación Fisiológica/fisiología , Muerte Celular/fisiología , Supervivencia Celular/fisiología , Colágeno/metabolismo , Implantación Dental Endoósea/métodos , Materiales Dentales/química , Retención de Prótesis Dentales , Módulo de Elasticidad , Fémur/lesiones , Fémur/cirugía , Análisis de Elementos Finitos , Masculino , Ratones , Oseointegración/fisiología , Osteocitos/patología , Osteogénesis/fisiología , Osteotomía/métodos , Docilidad , Estrés Mecánico , Propiedades de Superficie , Titanio/química , TorqueRESUMEN
To identify potential microRNA (miRNA) links between Smad3, a mediator of TGF-ß (transforming growth factor-ß) signaling, and E-cadherin, we characterized the miRNA profiles of two gastric cancer cell lines: SNU484-LPCX, which does not express Smad3, and SNU484-Smad3, in which Smad3 is overexpressed. We found that among differentially expressed miRNAs, miR-200 family members are overexpressed in SNU484-Smad3 cells. Subsequent studies, including analysis of the effects of silencing Smad3 in SNU484-Smad3 cells and a luciferase reporter assay, revealed that Smad3 directly binds to a Smad-binding element located in the promoter region of miR-200b/a, where it functions as a transcriptional activator. TGF-ß did not affect the regulatory role of Smad3 in transcription of miR-200 and expression of epithelial-mesenchymal transition markers. We conclude that Smad3 regulates, at the transcriptional level, miR-200 family members, which themselves regulate ZEB1 and ZEB2, known transcriptional repressors of E-cadherin, at the posttranscriptional level in a TGF-ß-independent manner. This represents a novel link between Smad3 and posttranscriptional regulation by miRNAs in epithelial-mesenchymal transition in gastric cancer cells.
Asunto(s)
Cadherinas/metabolismo , Transducción de Señal , Proteína smad3/metabolismo , Neoplasias Gástricas/metabolismo , Línea Celular Tumoral , Transición Epitelial-Mesenquimal , Regulación Neoplásica de la Expresión Génica , Humanos , MicroARNs/metabolismo , Factor de Crecimiento Transformador beta/metabolismoRESUMEN
FoxC1 is an important transcription factor in vertebrate development since its mutation in humans results in Axenfeld-Rieger syndrome. In the mouse, disturbance of its function causes congenital hydrocephalus and abnormalities in the development of various mesodermal derivatives. In this report, we provide one mechanistic basis for the requirement for FoxC1 in vertebrate development. We find that, in Xenopus laevis embryos, FoxC1 expression is regulated by the maternal T-box transcription factor VegT, via the nodal sub-family of TGFbeta signaling transducers. We show that at the late neurula to early tailbud stage, FoxC1 depletion causes the down-regulation of adhesion molecules, EP and E cadherin, as well as members of the Ephrin/EphR signaling families in the mesoderm germ layer resulting in the loss of adhesion and apoptosis of mesodermal cells.
Asunto(s)
Tipificación del Cuerpo , Factores de Transcripción Forkhead/metabolismo , Proteínas de Xenopus/metabolismo , Xenopus laevis/embriología , Xenopus laevis/genética , Animales , Tipificación del Cuerpo/genética , Cadherinas/genética , Cadherinas/metabolismo , Efrinas/genética , Efrinas/metabolismo , Factores de Transcripción Forkhead/genética , Gástrula/embriología , Regulación del Desarrollo de la Expresión Génica , Mesodermo/citología , Mesodermo/embriología , Mesodermo/metabolismo , Receptores de la Familia Eph/genética , Receptores de la Familia Eph/metabolismo , Proteínas de Dominio T Box/genética , Proteínas de Dominio T Box/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Proteínas de Xenopus/genética , Xenopus laevis/metabolismoRESUMEN
AIM: Fermented milk product containing edible mushroom water extracts (mushroom yogurt; MY) has been reported to have glycaemic control and triglyceride-lowering effects in streptozotocin (STZ)-induced diabetic rats and Zucker diabetic fatty (ZDF) rats. Here, we investigated how MY-supplemented dietary fibre (10 and 20%, v/w) influences the onset of obesity and hypertriglyceridaemia in Otsuka Long-Evans Tokushima fatty (OLETF) rats. METHODS: The OLETF rats were fed a powdered chow diet supplemented with MY at the levels of 10 (v/w) and 20% for 6 weeks from 10 weeks of age, but the OLETF control rats were not supplemented. Their weight, fat distribution and lipid profile have been determined. RESULTS: The body weights in MY-fed rats were reduced compared with the control rats. The perirenal fat was decreased in both MY groups, but the visceral and epididymal fats reduced only in the MY 20% group. The concentrations of serum triglyceride and non-esterified fatty acid in MY-fed rats were decreased in a dose-dependent manner. However, the levels of other serum lipid profiles [total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol] were comparable among all rats. CONCLUSION: Anti-obesity and triglyceride lowering by MY-supplemented dietary fibre in OLETF rats might have resulted from the synergistic effect of components in the fermented mushroom-milk product.
Asunto(s)
Agaricales , Hipertrigliceridemia/prevención & control , Obesidad/prevención & control , Fitoterapia/métodos , Yogur , Tejido Adiposo/patología , Animales , Fármacos Antiobesidad/uso terapéutico , Fibras de la Dieta/uso terapéutico , Lípidos/sangre , Masculino , Obesidad/sangre , Obesidad/patología , Extractos Vegetales/uso terapéutico , Ratas , Ratas Endogámicas OLETF , Aumento de Peso/efectos de los fármacosRESUMEN
The effect of dietary hesperetin on the hepatic lipid content and the enzyme activities involved in triacylglycerol (TG) synthesis in rats fed diets with or without 1% orotic acid (OA) was studied. Hepatic TG content was raised by approximately 5-fold after administration of OA for 10 days. The OA-feeding significantly increased the activity of hepatic microsomal phosphatidate phosphohydrolase (PAP), which is the rate-limiting enzyme for TG synthesis. Hepatic glucose-6-phosphate dehydrogenase (G6PDH) and malic enzyme activities were also increased. An addition of 1% hesperetin to the OA-supplemented diet resulted in the decrease of the hepatic TG content by 44% and of microsomal PAP activity. Dietary hesperetin alone neither affected liver TG content nor PAP activity significantly. OA-feeding caused an increased liver cholesterol level, whereas simultaneous addition of hesperetin and OA reduced its content to the control level. A slight reduction of hepatic cholesterol by hesperetin was also observed in the OA-free dietary group. The present study demonstrated that dietary hesperetin can reduce the hepatic TG accumulation induced by OA, and this was associated with the reduced activity of TG synthetic enzyme, PAP.
Asunto(s)
Flavonoides/farmacología , Hesperidina , Hígado/efectos de los fármacos , Hígado/metabolismo , Ácido Orótico/administración & dosificación , Fosfatidato Fosfatasa/metabolismo , Triglicéridos/metabolismo , Animales , Colesterol/sangre , Colesterol/metabolismo , Dieta , Ácidos Grasos/metabolismo , Flavonoides/administración & dosificación , Glucosafosfato Deshidrogenasa/metabolismo , Malato Deshidrogenasa/metabolismo , Masculino , Microsomas Hepáticos/efectos de los fármacos , Microsomas Hepáticos/enzimología , Ratas , Ratas Sprague-Dawley , Triglicéridos/sangreRESUMEN
Most orthodontic appliances and archwires are stainless steel or nickel-titanium (NiTi) alloys that can release metal ions, with saliva as the medium. To measure metal released from the fixed orthodontic appliances currently in use, we fabricated simulated fixed orthodontic appliances that corresponded to half of the maxillary arch and soaked them in 50 mL of artificial saliva (pH 6.75 +/- 0.15, 37 degrees C) for 3 months. We used brackets, tubes, and bands made by Tomy (Tokyo, Japan). Four groups were established according to the appliance manufacturer and the type of metal in the .016 x .022-in archwires. Groups A and B were stainless steel archwires from Ormco (Glendora, Calif) and Dentaurum (Ispringen, Germany), respectively, and groups C and D were both NiTi archwires with Ormco's copper NiTi and Tomy's Bioforce sentalloy, respectively. Stainless steel archwires were heat treated in an electric furnace at 500 degrees C for 1 minute and quenched in water. We measured the amount of metal released from each group by immersion time. Our conclusions were as follows: (1) there was no increase in the amount of chromium released after 4 weeks in group A, 2 weeks in group B, 3 weeks in group C, and 8 weeks in group D; (2) there was no increase in the amount of nickel released after 2 weeks in group A, 3 days in group B, 7 days in group C, and 3 weeks in group D; and (3) there was no increase in the amount of iron released after 2 weeks in group A, 3 days in group B, and 1 day in groups C and D. In our 3-month-long investigation, we saw a decrease in metal released as immersion time increased.
Asunto(s)
Metales/química , Níquel/química , Aparatos Ortodóncicos , Acero Inoxidable/química , Titanio/química , Cromo/química , Cobre/química , Inmersión , Iones , Hierro/química , Ensayo de Materiales , Modelos Dentales , Saliva Artificial , Factores de TiempoRESUMEN
A possible role of hepatocyte nuclear factor 1 (HNF1) or HNF3, a predominant trans-acting factors of hepatic or pancreatic beta-cells, was examined on the tissue specific interdependent expression of glucokinase (GK) in liver, H4IIE, HepG2, HIT-T15 and MIN6 cell line. The tissues or cell lines known to express GK showed abundant levels of HNF1 and HNF3 mRNA as observed in liver, H4IIE, HepG2, HIT-T15 and MIN6 cells, whereas they were not detected in brain, heart, NIH 3T3, HeLa cells. The promoter of glucokinase contains several HNF3 consensus sequences and are well conserved in human, mouse and rat. Transfection of the glucokinase promotor linked with luciferase reporter to liver or pancreatic beta cell lines showed high interacting activities with HNF1 and HNF3, whereas minimal activities were detected in the cells expressing very low levels of HNFs. The binding of HNF1 or HNF3 to the GK promoter genes was confirmed by electrophoretic mobility shift assay (EMSA). From these data, we propose that the expression of HNF1 and/or HNF3 may, in part, contribute to the tissue specific expression of GK
Asunto(s)
Proteínas de Unión al ADN/fisiología , Glucoquinasa/biosíntesis , Glucoquinasa/genética , Proteínas Nucleares/fisiología , Factores de Transcripción/fisiología , Células 3T3 , Animales , Northern Blotting , Línea Celular , Núcleo Celular/metabolismo , Células Cultivadas , Proteínas de Unión al ADN/genética , Genes Reporteros , Células HeLa , Factor Nuclear 1 del Hepatocito , Factor Nuclear 1-alfa del Hepatocito , Factor Nuclear 1-beta del Hepatocito , Factor Nuclear 3-beta del Hepatocito , Humanos , Hígado/metabolismo , Luciferasas/metabolismo , Ratones , Modelos Genéticos , Proteínas Nucleares/genética , Plásmidos/metabolismo , Regiones Promotoras Genéticas , Unión Proteica , Ratas , Distribución Tisular , Factores de Transcripción/genética , Transcripción Genética , TransfecciónRESUMEN
We identified the peroxisomal proliferator response element (PPRE) in the +68/+89 region of the rat GLUT2 gene. To identify whether the putative PPRE in the GLUT2 gene (GLUT2-PPRE) is functional, GLUT2 promoter-luciferase reporter constructs were transfected into CV-1 cells. Promoter activities were increased by coexpression of peroxisomal proliferator-activated receptor (PPAR)-gamma, retinoid X receptor (RXR)-alpha, and treatment of their ligands; troglitazone and 9-cis retinoic acid potentiated the transactivational effects. Introduction of mutations in GLUT2-PPRE resulted in loss of transactivational effects of the PPAR-gamma/RXR-alpha heterodimer. Electrophoretic mobility shift assay using nuclear extracts of CV-1 cells, which were transfected with various combinations of PPARs or RXR-alpha expression plasmids, revealed that heterodimers of PPAR-gamma and RXR-alpha preferentially bound to GLUT2-PPRE. In HIT-T15 cells, promoter activity of the rat GLUT2 gene was increased by troglitazone and 9-cis retinoic acid, and mutations of GLUT2-PPRE resulted in reduction of promoter activity. In addition, we observed increased GLUT2 transcription by troglitazone and 9-cis retinoic acid in isolated rat primary islets. These results suggested that the GLUT2-PPRE is functional and plays a significant role in gene expression of GLUT2 in pancreatic beta-cells. This is the first report identifying PPRE in a gene involved in glucose homeostasis, linking the effect of troglitazone on the regulation of insulin secretion.
Asunto(s)
Regulación de la Expresión Génica , Islotes Pancreáticos/metabolismo , Proteínas de Transporte de Monosacáridos/genética , Regiones Promotoras Genéticas , Receptores Citoplasmáticos y Nucleares/metabolismo , Tiazolidinedionas , Factores de Transcripción/metabolismo , Alitretinoína , Animales , Secuencia de Bases , Línea Celular , Células Cultivadas , Cromanos/farmacología , Secuencia de Consenso , Proteínas de Unión al ADN/química , Proteínas de Unión al ADN/metabolismo , Dimerización , Regulación de la Expresión Génica/efectos de los fármacos , Transportador de Glucosa de Tipo 2 , Hipoglucemiantes/farmacología , Islotes Pancreáticos/efectos de los fármacos , Masculino , Multimerización de Proteína , Ratas , Ratas Sprague-Dawley , Receptores Citoplasmáticos y Nucleares/química , Receptores Citoplasmáticos y Nucleares/genética , Receptores de Ácido Retinoico/metabolismo , Proteínas Recombinantes de Fusión/biosíntesis , Proteínas Recombinantes/metabolismo , Receptores X Retinoide , Alineación de Secuencia , Tiazoles/farmacología , Factores de Transcripción/química , Factores de Transcripción/genética , Transcripción Genética/efectos de los fármacos , Transfección , Tretinoina/farmacología , TroglitazonaRESUMEN
We investigated transacting factors binding to the cis-element important in tissue-specific expression of the human glucose transporter type 2 isoform (GLUT2) gene. By transient transfection assay, we determined that the 227-base pair fragment upstream of the ATG start site contained promoter activity and that the region from +87 to +132 (site C) was responsible for tissue-specific expression. DNase I footprinting and electrophoretic mobility shift assay indicated that site C contained one binding site for hepatocyte nuclear factor 1 (HNF1) and two binding sites for HNF3. The mutations at positions +101 and +103, which are considered to be critical in binding HNF1 and HNF3, resulted in a 53% decrease in promoter activity, whereas the mutation of the proximal HNF3 binding site (+115 and +117) reduced promoter activity by 28%. The mutations of these four sites resulted in marked decrease (70%) in promoter activity as well as diminished bindings of HNF1 and HNF3. A to G mutation, which causes conversion of the HNF1 and HNF3 binding sequence to the NF-Y binding site, resulted in a 22% decrease in promoter activity. We identified that both HNF1 and HNF3 function as transcriptional activators in GLUT2 gene expression. Coexpression of the pGL+74 (+74 to +301) construct with the HNF1alpha and HNF3beta expression vectors in NIH 3T3 cells showed the synergistic effect on GLUT2 promoter activity compared with the expression of HNF1alpha, HNF3beta, or a combination of HNF1beta and HNF3beta. These data suggest that HNF1alpha and HNF3beta may be the most important players in the tissue-specific expression of the human GLUT2 gene.
Asunto(s)
Proteínas de Unión al ADN/fisiología , Regulación de la Expresión Génica , Proteínas de Transporte de Monosacáridos/genética , Proteínas Nucleares/fisiología , Factores de Transcripción/fisiología , Activación Transcripcional , Secuencia de Bases , Proteínas Potenciadoras de Unión a CCAAT , Células Cultivadas , Secuencia de Consenso , Proteínas de Unión al ADN/metabolismo , Diabetes Mellitus Tipo 1/genética , Transportador de Glucosa de Tipo 2 , Factor Nuclear 1 del Hepatocito , Factor Nuclear 1-alfa del Hepatocito , Factor Nuclear 1-beta del Hepatocito , Factor Nuclear 3-beta del Hepatocito , Humanos , Datos de Secuencia Molecular , Proteínas de Transporte de Monosacáridos/biosíntesis , Regiones Promotoras GenéticasRESUMEN
The effects of dietary alpha-linolenic, eicosapentaenoic and docosahexaenoic acids on the enzyme activities related to hepatic lipogenesis and beta-oxidation were compared under constant polyunsaturated/monounsaturated/saturated fatty acids and n-6/n-3 ratios of dietary fats in rats. Dietary fat containing linoleic acid as the sole polyunsaturated fatty acid (PUFA) was also given as a control. The concentration of serum triglyceride and phospholipid in the three n-3 PUFA groups was lower than in the linoleic acid group. The hepatic triglyceride concentration was lower and the phospholipid concentration was higher in the three n-3 PUFA groups than in the linoleic acid group. Cytosolic fatty acid synthase (FAS) activity was lower in the n-3 PUFA groups than in the linoleic acid group, the reduction being more predominant in the eicosapentaenoic acid and docosahexaenoic acid groups than in the alpha-linolenic acid group. The cytosolic activities of the NADPH-generating enzymes, glucose-6-phosphate dehydrogenase (G6PDH) and the malic enzyme, were lower in the three n-3 PUFA groups. The activity of carnitine palmitoyltransferase (CPT) in mitochondria was higher only in the eicosapentaenoic acid group than in the other groups. The activity of Mg(2+)-dependent phosphatidate phosphohydrolase (PAP) in microsomes and cytosol was lower in the eicosapentaenoic and docosahexaenoic acid groups than in the linoleic acid group, while there was no effect of dietary fats on the activities of diacylglycerol acyltransferase (DGAT) and glycerol-3-phosphate acyltransferase (G3PAT) in microsomes. The CTP: phosphocholine cytidylyltransferase (CT) activity in the homogenate was lower in the n-3 PUFA groups, the reduction being more prominent in the eicosapentaenoic and docosahexaenoic acid groups than in the alpha-linolenic acid group. The choline kinase (CK) activity in cytosol was lower in the eicosapentaenoic acid group than in the linoleic acid group. These results showed that dietary alpha-linolenic, eicosapentaenoic and docosahexaenoic acids differently influenced hepatic lipogenesis and the partition of fatty acid into oxidation or glycerolipid synthesis.
Asunto(s)
Dieta , Ácidos Docosahexaenoicos/farmacología , Ácido Eicosapentaenoico/farmacología , Lípidos/biosíntesis , Hígado/metabolismo , Ácido alfa-Linolénico/farmacología , Animales , Lípidos/sangre , Hígado/efectos de los fármacos , Hígado/enzimología , Masculino , Tamaño de los Órganos/efectos de los fármacos , Oxidación-Reducción , Ratas , Ratas Sprague-Dawley , Fracciones Subcelulares/efectos de los fármacos , Fracciones Subcelulares/metabolismo , Aumento de Peso/efectos de los fármacosRESUMEN
Protein kinase CKII (CKII) is a ubiquitous protein serine/threonine kinase. CKII usually exists in tetrameric complexes composed of two catalytic (CKII alpha and/or CKII alpha') and two regulatory (CKII beta) subunits. In the present study, using a combined in vivo and in vitro approach, we have investigated the role of CKII subunits in the formation of the tetrameric structure of CKII and the formation of the polymeric structure of CKII holoenzyme. Our in vivo experiments show that CKII beta interacts with either another CKII beta or CKII alpha and that CKII alpha does not interact with another CKII alpha (or CKII alpha'). Our in vitro experiments also show that CKII beta is able to associate with both CKII alpha and another CKII beta and that CKII alpha exists as a monomeric form in solution. These data indicate that CKII beta mediates the formation of a tetramer by both the dimerization of CKII beta and the interaction of CKII beta with CKII alpha. The results of this study also suggest that CKII beta may be involved in the formation of the polymeric structure of the CKII holoenzyme.
Asunto(s)
Proteínas Serina-Treonina Quinasas/química , Proteínas Serina-Treonina Quinasas/metabolismo , Quinasa de la Caseína II , Coenzimas/química , Coenzimas/metabolismo , Dimerización , Escherichia coli/enzimología , Escherichia coli/genética , Humanos , Concentración Osmolar , Polímeros/química , Polímeros/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Saccharomyces cerevisiae/enzimología , Saccharomyces cerevisiae/genética , Sales (Química)RESUMEN
Orotic acid is known to cause fatty liver, but it is unclear whether this is caused partly by stimulation of the enzymes for triacylglycerol (TG) synthesis. To understand the change of hepatic TG metabolism in fatty liver induced by orotic acid, we determined the liver tissue TG level and phosphatidate phosphohydrolase (PAP) activity over time in rats fed on a diet containing orotic acid (OA). A dietary lipid content of 10% was achieved by using n-6 fatty acid-rich corn oil in experiment 1, and n-6 fatty acid-rich safflower oil (SO) and n-3 fatty acid-rich fish oil (FO) with the same polyunsaturated fatty acid/monounsaturated fatty acid/saturated fatty acid (P/M/S) ratio in experiment 2. In experiment 1, an increase in the hepatic TG level due to OA intake was observed from day 5 onwards, the level rising approximately 6-fold by day 10. The activity of hepatic microsomal PAP, the rate-limiting enzyme in TG synthesis, increased markedly from day 5 onwards, concurrent with the liver diacylglycerol concentration. A strong correlation (r = 0.974) was observed between the hepatic TG level and microsome-bound PAP activity. In experiment 2, we investigated the effects of dietary fatty acid on OA-induced fatty liver. Compared with the n-6 fatty acid-rich vegetable oil diet, the relative increase in hepatic TG was smaller with the n-3 fatty acid-rich FO diet, and hepatic PAP activity fell markedly to the level for an OA-free diet. In addition, the hepatic TG accumulation and serum TG concentration were lower in the FO group than in the SO group. Nevertheless, because the hepatic TG level was low, it seems that the inhibition of liver PAP activity by FO possibly had a strong influence on the accumulation of TG in the liver. In conclusion, enhanced TG synthesis mediated by changes in liver PAP activity was involved in the hepatic TG accumulation induced by OA administration, this change being markedly suppressed by dietary n-3 fatty acids.
Asunto(s)
Hígado/efectos de los fármacos , Hígado/metabolismo , Ácido Orótico/toxicidad , Fosfatidato Fosfatasa/metabolismo , Triglicéridos/metabolismo , Animales , Dieta , Ácidos Grasos Omega-3/farmacología , Ácidos Grasos Omega-6 , Ácidos Grasos Insaturados/farmacología , Hígado Graso/inducido químicamente , Hígado Graso/metabolismo , Masculino , Ratas , Ratas Sprague-Dawley , Triglicéridos/sangreRESUMEN
The pharmacological effects of Oren-gedoku-to (OGT), a Japanese-Chinese traditional herbal medicinal mixture on lipid biosynthesis were investigated in cultured human hepatocyte HepG2 cells. The addition of OGT (0.5 and 4.2 mg/ml), which had no effect on cell proliferation and cellular protein content, caused a marked decrease in the cellular cholesterol content, particularly cholesteryl ester content following 24 h incubation. The incorporation of 14C-oleate into cellular cholesteryl ester fraction was also reduced remarkably during incubation for 6 and 24 h. The effects of OGT, its components and its main active chemicals on acyl-coenzyme A:cholesterol acyltransferase (ACAT) activity were studied in vitro to explore the mechanism by which OGT inhibits cholesteryl ester formation. The data confirmed that OGT, in a dose-dependent manner, and its components (Scutellaria baicalensis, Coptis japonica, Gardenia jasminoides and Phellodendron amurense) remarkably inhibit ACAT activity. Among the main active chemicals of OGT, baicalein, a kind of flavonoid, decreased ACAT activity in a dose-dependent fashion from the level of 10(-6)M. These results strongly suggest that OGT reduces the cholesteryl ester formation in human hepatocytes by inhibiting ACAT, and that baicalein may, in part, be responsible for ACAT inhibition.
Asunto(s)
Ésteres del Colesterol/biosíntesis , Medicamentos Herbarios Chinos/farmacología , Hígado/efectos de los fármacos , Plantas Medicinales/química , Esterol O-Aciltransferasa/metabolismo , Radioisótopos de Carbono , División Celular/efectos de los fármacos , Línea Celular , Colesterol/metabolismo , Medicamentos Herbarios Chinos/química , Inhibidores Enzimáticos/farmacología , Humanos , Hígado/citología , Hígado/enzimología , Esterol O-Aciltransferasa/antagonistas & inhibidoresRESUMEN
Casein kinase II (CKII) usually exists as a heterotetramer with alpha 2 beta 2, alpha alpha'beta 2, or alpha'2 beta 2. The alpha or alpha' subunits catalyze protein phosphorylation, whereas the function of the beta subunit remains unclear. One of the possible functions of the beta subunit may be to mediate the interaction of the catalytic subunit with target proteins. To identify proteins capable of associating with the beta subunit in vivo, we have used a two-hybrid system. One protein identified is human ribosomal protein L5. The protein L5 does not interact with the alpha or alpha' subunits of CKII, supporting the idea that the beta subunit can determine a substrate specificity of CKII. These results furthermore suggest a novel role for CKII in ribosomal L5 phosphorylation, in ribosomal assembly, or ribosomal transport in the intact cells. The protein L5 may act as a regulator of the activity or subcellular localization of CKII.
Asunto(s)
Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Ribosómicas/metabolismo , Secuencia de Aminoácidos , Secuencia de Bases , Quinasa de la Caseína II , Cartilla de ADN , Humanos , Datos de Secuencia Molecular , Unión Proteica , Homología de Secuencia de Aminoácido , Homología de Secuencia de Ácido NucleicoRESUMEN
Necrotizing fasciitis is a rare, often fatal soft tissue infection. It still remains a confusing entity because of the nomenclature and multiple subtypes described in the past. An interesting case study of a patient with necrotizing fasciitis secondary to nonclostridial gas gangrene is presented. A comprehensive review of necrotizing fasciitis, its disease process and treatment modalities will be discussed.