类固醇合成急性调节相关脂质转运蛋白3(steroidogenic acute regulatory protein related lipid transfer domain containing3,STARD3)是类固醇激素急性调节蛋白家族成员之一,参与细胞内胆固醇非囊泡转运过程。目前已有研究证明人类表...类固醇合成急性调节相关脂质转运蛋白3(steroidogenic acute regulatory protein related lipid transfer domain containing3,STARD3)是类固醇激素急性调节蛋白家族成员之一,参与细胞内胆固醇非囊泡转运过程。目前已有研究证明人类表皮生长因子受体2(human epidermal growth factor receptor 2,HER2)阳性乳腺癌的STARD3基因可与HER2基因共扩增、共高表达,且STARD3表达水平与肿瘤转移、局部复发和较短的总生存期呈正相关。本文就STARD3调节细胞内胆固醇分配过程以及与HER2阳性乳腺癌的关系进行综述,并分析其可能的致病机制。展开更多
AIM: To examine the in vivo phenotype associated with hepatic metastatic lymph node 64 (MLN64) overexpression.METHODS: Recombinant-adenovirus-mediated MLN64 gene transfer was used to overexpress MLN64 in the liver...AIM: To examine the in vivo phenotype associated with hepatic metastatic lymph node 64 (MLN64) overexpression.METHODS: Recombinant-adenovirus-mediated MLN64 gene transfer was used to overexpress MLN64 in the livers of C57BL/6 mice. We measured the effects of MLN64 overexpression on hepatic cholesterol content, bile flow, biliary lipid secretion and apoptosis markers. For in vitro studies cultured CHO cells with transient MLN64 overexpression were utilized and apoptosis by TUNEL assay was measured.RESULTS: Livers from Ad.MLN64-infected mice exhibited early onset of liver damage and apoptosis. This response correlated with increases in liver cholesterol content and bilian/bile acid concentration, and impaired bile flow. We investigated whether liver MLN64 expression could be modulated in a murine model of hepatic injury. We found increased hepatic MLN64 mRNA and protein levels in mice with chenodeoxycholic acid-induced liver damage. In addition, cultured CliO cells with transient MLN64 overexpression showed increased apoptosis.CONCLUSION: In summary, hepatic MLN64 overexpression induced damage and apoptosis in murine livers and altered cholesterol metabolism. Further studies are required to elucidate the relevance of these findings under physiologic and disease conditions.展开更多
文摘类固醇合成急性调节相关脂质转运蛋白3(steroidogenic acute regulatory protein related lipid transfer domain containing3,STARD3)是类固醇激素急性调节蛋白家族成员之一,参与细胞内胆固醇非囊泡转运过程。目前已有研究证明人类表皮生长因子受体2(human epidermal growth factor receptor 2,HER2)阳性乳腺癌的STARD3基因可与HER2基因共扩增、共高表达,且STARD3表达水平与肿瘤转移、局部复发和较短的总生存期呈正相关。本文就STARD3调节细胞内胆固醇分配过程以及与HER2阳性乳腺癌的关系进行综述,并分析其可能的致病机制。
基金Fondo Nacional de Desarrollo Científico y Tecnológico, FONDECYT grant No. 1030415 to S.Z. and No. 1030416 to A.R.
文摘AIM: To examine the in vivo phenotype associated with hepatic metastatic lymph node 64 (MLN64) overexpression.METHODS: Recombinant-adenovirus-mediated MLN64 gene transfer was used to overexpress MLN64 in the livers of C57BL/6 mice. We measured the effects of MLN64 overexpression on hepatic cholesterol content, bile flow, biliary lipid secretion and apoptosis markers. For in vitro studies cultured CHO cells with transient MLN64 overexpression were utilized and apoptosis by TUNEL assay was measured.RESULTS: Livers from Ad.MLN64-infected mice exhibited early onset of liver damage and apoptosis. This response correlated with increases in liver cholesterol content and bilian/bile acid concentration, and impaired bile flow. We investigated whether liver MLN64 expression could be modulated in a murine model of hepatic injury. We found increased hepatic MLN64 mRNA and protein levels in mice with chenodeoxycholic acid-induced liver damage. In addition, cultured CliO cells with transient MLN64 overexpression showed increased apoptosis.CONCLUSION: In summary, hepatic MLN64 overexpression induced damage and apoptosis in murine livers and altered cholesterol metabolism. Further studies are required to elucidate the relevance of these findings under physiologic and disease conditions.