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首页> 外文期刊>Endocrine journal >Possible Involvement of Atypical Protein Kinase C (PKC) in Glucose-Sensitive Expression of the Human Insulin Gene: DNA-Binding Activity and Transcriptional Activity of Pancreatic and Duodenal Homeobox Gene-1 (PDX-1) Are Enhanced via Calphostin C-Sensitive but Phorbol 12-Myristate 13-Acetate (PMA) and Gö 6976-Insensitive Pathway
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Possible Involvement of Atypical Protein Kinase C (PKC) in Glucose-Sensitive Expression of the Human Insulin Gene: DNA-Binding Activity and Transcriptional Activity of Pancreatic and Duodenal Homeobox Gene-1 (PDX-1) Are Enhanced via Calphostin C-Sensitive but Phorbol 12-Myristate 13-Acetate (PMA) and Gö 6976-Insensitive Pathway

机译：非典型蛋白激酶C（PKC）可能参与人类胰岛素基因的葡萄糖敏感性表达：胰钙和十二指肠同源盒基因-1（PDX-1）的DNA结合活性和转录活性通过钙磷蛋白C敏感性增强但由佛波醇12-肉豆蔻酸13-醋酸酯（PMA）和Gö6976-不敏感途径

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References(68) Cited-By(28) Pancreatic and duodenal homeobox gene-1(PDX-1) is a transcription factor which regulates the insulin gene expression. In this study, we tried to elucidate the role of PDX-1 in the glucose-induced transcriptional activation of the human insulin gene promoter in MINE cells. Electrophoretic mobility shift assay (EMSA) and chloramphenicol acetyltransferase (CAT) assay demonstrated that both DNA-binding activity and transcriptional activity of PDX-1 were increased with 20mmol/l glucose more than with 2mmol/l glucose. The DNA-binding activity of PDX-1 induced by high glucose was blocked by phosphatase treatment, suggesting the involvement of PDX-1 phosphorylation in this event. In an in vitro phosphorylation study, PDX-1 was phosphorylated by protein kinase C (PKC), but not by cAMP dependent protein kinase (PKA) or mitogen-activated protein kinase (MAPK). Furthermore, increased PDX-1 function induced by high glucose was blocked by calphostin C, an inhibitor of all PKC isoforms, but unaffected by phorbol 12-myristate 13-acetate (PMA), an activator of classical and novel PKC, or Gö 6976, an inhibitor of classical and novel PKC, which suggested that the PKC family which activated PDX-1 in MINE cells was atypical PKC. Western blot and immunocytochemical studies with anti-PKCζ antibody confirmed the presence of PKC ζ, one of the isoforms of atypical PKC, in MIN6 cells. Furthermore, PKC ζ activity was significantly increased by glucose stimulation. These results suggest that high glucose increased DNA-binding activity of PDX-1 by activating atypical PKC including PKC ζ, resulting in transcriptional activation of the human insulin gene promoter.
机译：参考文献（68）Cited-By（28）胰和十二指肠同源盒基因-1（PDX-1）是调节胰岛素基因表达的转录因子。在这项研究中，我们试图阐明PDX-1在MINE细胞中葡萄糖诱导的人类胰岛素基因启动子的转录激活中的作用。电泳迁移率迁移分析（EMSA）和氯霉素乙酰转移酶（CAT）分析表明，PDX-1的DNA结合活性和转录活性在20mmol / l葡萄糖下比在2mmol / l葡萄糖下增加。高葡萄糖诱导的PDX-1的DNA结合活性被磷酸酶处理所阻断，表明PDX-1磷酸化参与了这一事件。在一项体外磷酸化研究中，PDX-1被蛋白激酶C（PKC）磷酸化，但不被cAMP依赖性蛋白激酶（PKA）或有丝分裂原激活的蛋白激酶（MAPK）磷酸化。此外，由高葡萄糖诱导的PDX-1功能增强被钙磷蛋白C阻止，钙磷蛋白C是所有PKC亚型的抑制剂，但不受经典和新型PKC的活化剂佛波12-肉豆蔻酸酯13-乙酸酯（PMA）或Gö6976的影响， PKC是经典和新型PKC的抑制剂，这表明激活MINE细胞中PDX-1的PKC家族是非典型PKC。用抗PKCζ抗体进行的蛋白质印迹和免疫细胞化学研究证实，MIN6细胞中存在非典型PKC异构体之一PKCζ。此外，葡萄糖刺激显着增加了PKCζ活性。这些结果表明，高葡萄糖通过激活包括PKCζ在内的非典型PKC来增加PDX-1的DNA结合活性，从而导致人胰岛素基因启动子的转录激活。

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