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Ca2+ signal stimulates the expression of steroidogenic acute regulatory protein and steroidogenesis in bovine adrenal fasciculata-reticularis cells

机译:Ca2 +信号刺激牛肾上腺筋膜网状细胞中类固醇生成的急性调节蛋白的表达和类固醇生成

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Adrenal glucocorticoid synthesis is stimulated by ACTH or its nitrophenylsulphenyl derivative, NPS-ACTH. Acute stimulation of steroid hormone biosynthesis is highly dependent on the expression of steroidogenic acute regulatory (StAR) protein. To determine the regulatory mechanism of StAR expression in bovine fasciculata/reticularis cells, we analyzed the second messenger systems involved in StAR protein expression using cultured cells activated by ACTH and NPS-ACTH. We concluded that cAMP is not the essential second messenger for StAR protein expression, since NPS-ACTH activated StAR protein expression more than ACTH without increase in cellular cAMP. A 15-lipoxygenase metabolite(s) of arachidonic acid stimulated steroidogenesis without increase in StAR protein expression, since AA-861, a lipoxygenase inhibitor, inhibited steroidogenesis without affecting StAR protein expression. Stimulation of StAR protein expression and the corresponding increase in the steroidogenesis were inhibited by nicardipine in cells treated with ACTH or NPS-ACTH. These data indicate that the dominant second messenger for the stimulation of StAR protein expression is Ca2+. Calmodulin-dependent kinase 11 inhibitors KN-93 and KN-62 suppressed steroidogenic activity without affecting StAR expression. The protein kinase C inhibitor Ro 31-8220 did not show any effects on StAR expression and steroidogenesis. Calmodulin-dependent kinase 11 and protein kinase C can therefore be concluded not to be involved in StAR protein expression in bovine cells. (c) 2005 Elsevier Inc. All rights reserved.
机译:肾上腺糖皮质激素的合成受到ACTH或其硝基苯基磺苯基衍生物NPS-ACTH的刺激。甾类激素生物合成的急性刺激高度依赖于类固醇生成的急性调节(StAR)蛋白的表达。为了确定StAR在牛筋膜/网状细胞中表达的调控机制,我们使用由ACTH和NPS-ACTH激活的培养细胞分析了参与StAR蛋白表达的第二信使系统。我们得出的结论是,cAMP不是StAR蛋白表达的必要第二信使,因为NPS-ACTH比ACTH激活的StAR蛋白表达更多,而不会增加细胞cAMP。花生四烯酸的一种15-脂氧合酶代谢产物可刺激类固醇生成而不会增加StAR蛋白的表达,因为脂氧合酶抑制剂AA-861可抑制类固醇生成而不会影响StAR蛋白的表达。尼卡地平在ACTH或NPS-ACTH处理的细胞中抑制了StAR蛋白表达的刺激和类固醇生成的相应增加。这些数据表明,刺激StAR蛋白表达的主要第二信使是Ca2 +。钙调蛋白依赖性激酶11抑制剂KN-93和KN-62抑制类固醇生成活性,而不会影响StAR表达。蛋白激酶C抑制剂Ro 31-8220对StAR表达和类固醇生成没有任何影响。因此,可以得出钙调蛋白依赖性激酶11和蛋白激酶C不参与牛细胞中StAR蛋白表达的结论。 (c)2005 Elsevier Inc.保留所有权利。

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