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Sterol Regulatory Element Binding Protein (sterol + regulatory_element_binding_protein)
Selected AbstractsAssociation of a Polymorphism in the Intron 7 of the SREBF1 Gene with Osteonecrosis of the Femoral Head in KoreansANNALS OF HUMAN GENETICS, Issue 1 2009H.-J. Lee Summary Reduction or disruption of the blood supply to the bone is involved in the pathogenesis of osteonecrosis of the femoral head (ONFH). An altered lipid metabolism is one of the major risk factors for ONFH. Sterol regulatory element binding protein, SREBF1 activates genes regulating lipid biosynthesis. The aim of this study was to examine the association between the polymorphisms of the SREBF1 gene and ONFH susceptibility in the Korean population. The SREBF1 gene in 24 unrelated Korean individuals was sequenced and two polymorphisms were detected. Two variants, IVS6 , 48 C > T and IVS7 + 117 A > G, were genotyped in 423 ONFH patients and 348 controls. The genotype frequency of IVS7 + 117 A > G in ONFH patients was significantly different from that of the control group with P value < 0.0001 (Adjusted OR; 6.88, 95% CI; 3.74-12.67). Moreover, the IVS7 + 117 A > G genotype showed an association with men, and further analysis stratified by etiological factors indicated that the genotype data was significantly associated with a high risk for patients with alcohol-induced ONFH (P < 0.0001). We found that the IVS7 + 117 A > G polymorphism of the SREBF1 gene is associated with an increased risk of ONFH in the Korean population. [source] A common variant in the patatin-like phospholipase 3 gene (PNPLA3) is associated with fatty liver disease in obese children and adolescents,,HEPATOLOGY, Issue 4 2010Nicola Santoro The genetic factors associated with susceptibility to nonalcoholic fatty liver disease (NAFLD) in pediatric obesity remain largely unknown. Recently, a nonsynonymous single-nucleotide polymorphism (rs738409), in the patatin-like phospholipase 3 gene (PNPLA3) has been associated with hepatic steatosis in adults. In a multiethnic group of 85 obese youths, we genotyped the PNLPA3 single-nucleotide polymorphism, measured hepatic fat content by magnetic resonance imaging and insulin sensitivity by the insulin clamp. Because PNPLA3 might affect adipogenesis/lipogenesis, we explored the putative association with the distribution of adipose cell size and the expression of some adipogenic/lipogenic genes in a subset of subjects who underwent a subcutaneous fat biopsy. Steatosis was present in 41% of Caucasians, 23% of African Americans, and 66% of Hispanics. The frequency of PNPLA3(rs738409) G allele was 0.324 in Caucasians, 0.183 in African Americans, and 0.483 in Hispanics. The prevalence of the G allele was higher in subjects showing hepatic steatosis. Surprisingly, subjects carrying the G allele showed comparable hepatic glucose production rates, peripheral glucose disposal rate, and glycerol turnover as the CC homozygotes. Carriers of the G allele showed smaller adipocytes than those with CC genotype (P = 0.005). Although the expression of PNPLA3, PNPLA2, PPAR,2(peroxisome proliferator-activated receptor gamma 2), SREBP1c(sterol regulatory element binding protein 1c), and ACACA(acetyl coenzyme A carboxylase) was not different between genotypes, carriers of the G allele showed lower leptin (LEP)(P = 0.03) and sirtuin 1 (SIRT1) expression (P = 0.04). Conclusion: A common variant of the PNPLA3 gene confers susceptibility to hepatic steatosis in obese youths without increasing the level of hepatic and peripheral insulin resistance. The rs738409 PNPLA3 G allele is associated with morphological changes in adipocyte cell size. (HEPATOLOGY 2010.) [source] Mechanisms of protection by the betaine-homocysteine methyltransferase/betaine system in HepG2 cells and primary mouse hepatocytes,HEPATOLOGY, Issue 5 2007Cheng Ji Betaine-homocysteine methyltransferase (BHMT) regulates homocysteine levels in the liver. We previously reported that the alteration of BHMT is associated with alcoholic liver steatosis and injury. In this study, we tested whether BHMT protects hepatocytes from homocysteine-induced injury and lipid accumulation. Both BHMT transfectants of HepG2 cells and primary mouse hepatocytes with suppressed BHMT were generated. Comparisons were made between the cell models with respect to their response to homocysteine treatments. Homocysteine metabolism was impaired in HepG2 cells, and the expression of BHMT in HepG2 cells ameliorated the impairment and stabilized the levels of intracellular homocysteine after the addition of exogenous homocysteine. BHMT expression inhibited homocysteine-induced glucose-regulated protein 78 (GRP78) and C/EBP-homologous protein (CHOP) and homocysteine-induced cell death. A betaine treatment protected primary mouse hepatocytes from a homocysteine-induced increase in GRP78 and cell death but not a tunicamycin-induced increase. Homocysteine induced greater CHOP expression (2.7-fold) in BHMT small interfering RNA (siRNA),transfected cells than in a control (1.9-fold). Homocysteine-induced cell death was increased by 40% in the siRNA-treated cells in comparison with the control. Apolipoprotein B (apoB) expression was higher and triglycerides and cholesterol were lower in HepG2 expressing BHMT. In primary mouse hepatocytes, homocysteine induced the accumulation of triglycerides and cholesterol, which was reduced in the presence of betaine. Betaine partially reduced homocysteine-induced sterol regulatory element binding protein 1 expression in HepG2 cells and increased S-adenosylmethionine in primary mouse hepatocytes. Conclusion: The BHMT/betaine system directly protects hepatocytes from homocysteine-induced injury but not tunicamycin-induced injury, including an endoplasmic reticulum stress response, lipid accumulation, and cell death. This system also exhibits a more generalized effect on liver lipids by inducing ApoB expression and increasing S-adenosylmethionine/S-adenosylhomocysteine. (HEPATOLOGY 2007.) [source] Inhibition of low density lipoprotein receptor expression by long-term exposure to phorbol ester via p38 mitogen-activated protein kinase pathwayJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 4 2005Jiyoung Oh Abstract The proximal region ,234 to (+58 bp) of low-density lipoprotein receptor (LDLR) is responsible for its up-regulation by sterol regulatory element binding protein (SREBP). However, the mechanism of sterol-independent repression of LDLR has not been determined yet. In this study, we observed that there was an early induction and a later repression of LDLR by phorbol ester (PMA) in SK-Hep1 hepatocarcinoma cells and investigated the mechanisms through which PMA repressed LDLR transcription. SK-Hep1 cells were exposed to PMA and LDLR mRNA was evaluated by RT-PCR and Northern blot analysis. The effect of phorbol ester on LDLR transcriptional activity was studied using transient transfection of LDLR promoter-luciferase constructs. Overexpression of N-SREBP-2, a dominant positive SREBP2, did not reverse the PMA-repressed LDLR promoter activity. Serial deletion of LDLR promoter revealed that the region between ,1,563 and ,1,326 was responsible for the repression. The pretreatment with SB202190, an inhibitor for p38 mitogen-activated protein kinase pathway (p38-MAPK), but not other signaling inhibitors, reversed the PMA-induced repression. The 24 h-treatment with PMA efficiently arrested the SK-Hep1 cell cycle at G0/G1 as demonstrated by FACS analysis and decreased the 3H-thymidine incorporation. The PMA-induced repression of LDLR transcription may be exerted by the factor(s), not SREBP2, induced or modified by p38-MAPK-mediated signaling pathway and associated with cell cycle blockage. © 2005 Wiley-Liss, Inc. [source] Effect of SCD and SREBP genotypes on fatty acid composition in adipose tissue of Japanese Black cattle herdsANIMAL SCIENCE JOURNAL, Issue 3 2009Hideki OHSAKI ABSTRACT Fatty acid composition of beef adipose tissue is one of important traits because high proportions of monounsaturated fatty acid are related to favorable beef flavor and tenderness. In this study, we investigated effects of genetic factors such as stearoyl-CoA desaturase (SCD) and sterol regulatory element binding protein (SREBP) on beef carcass traits including fatty acid composition using two cattle populations. Sire effect was significantly related to almost all traits except BMS, suggesting that the trait examined in this study is highly controlled by genetic factors. The effect of SCD genotype on fatty acid composition was detected remarkably in both cattle groups, especially on stearic and oleic acids. This result was consistent with our previous studies and suggests that SCD is associated with fatty acid composition. Unlike SCD genotyping, the effect of SREBP genotype was not identified in this study. Our results suggested that SCD genotype would contribute to improving beef quality in field populations. Further studies about the relationship among these factors will bring an insight into the molecular mechanism of fatty acid metabolism in cattle. [source] | ||||||||||