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高糖上调CYP24A1的表达,这减弱了1,25(OH)2D3在大鼠雪旺细胞系RSC96中增加神经生长因子(NGF)分泌的能力。

High glucose upregulates CYP24A1 expression which attenuates the ability of 1,25(OH)2D3 to increase NGF secretion in a rat Schwann cell line RSC96.

作者信息

Zhou Yi-Kun, Liang Zhi, Guo Yan, Zhang Hua-Tang, Wang Kun-Hua

机构信息

Department of Endocrinology and Metabolism, First People's Hospital of Yunnan Province (The Kunhua Affiliated Hospital of Kunming University of Science and Technology), Kunming, Yunnan, China.

Department of Information Center, First People's Hospital of Yunnan Province (The Kunhua Affiliated Hospital of Kunming University of Science and Technology), Kunming, Yunnan, China.

出版信息

Mol Cell Endocrinol. 2015 Mar 15;404:75-81. doi: 10.1016/j.mce.2015.01.005. Epub 2015 Jan 20.

Abstract

Vitamin D deficiency or insufficiency is an independent risk factor for diabetic peripheral neuropathy (DPN), but the relationship between 1,25(OH)2D3 and DPN remains unknown. We found that 1,25(OH)2D3 stimulated the secretion of nerve growth factor (NGF) in rat Schwann cell line RSC96, but ability of 1,25(OH)2D3 to increase NGF protein was impaired under high glucose conditions. High glucose upregulated the expression of CYP24A1 protein, which catalyzes the conversion of 1,25(OH)2D3 into inactive products, further impairing the ability of 1,25(OH)2D3 to upregulate NGF secretion in Schwann cells. Inhibition of CYP24A1 protein expression ameliorated the secretion of NGF in response to 1,25(OH)2D3. The findings of this study suggest that CYP24A1 protein plays an important role in the relationship between DPN and 1,25(OH)2D3.

摘要

维生素D缺乏或不足是糖尿病周围神经病变(DPN)的独立危险因素,但1,25(OH)₂D₃与DPN之间的关系尚不清楚。我们发现1,25(OH)₂D₃刺激大鼠雪旺细胞系RSC96中神经生长因子(NGF)的分泌,但在高糖条件下1,25(OH)₂D₃增加NGF蛋白的能力受损。高糖上调了CYP24A1蛋白的表达,该蛋白催化1,25(OH)₂D₃转化为无活性产物,进一步损害了1,25(OH)₂D₃上调雪旺细胞中NGF分泌的能力。抑制CYP24A1蛋白表达可改善对1,25(OH)₂D₃的反应中NGF的分泌。本研究结果表明,CYP24A1蛋白在DPN与1,25(OH)₂D₃的关系中起重要作用。

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