六价铬通过下调细胞周期蛋白依赖性激酶 (CDK) 和细胞周期蛋白，上调 CDK 抑制剂，从而阻止细胞周期并减少颗粒细胞增殖。

Chromium-VI arrests cell cycle and decreases granulosa cell proliferation by down-regulating cyclin-dependent kinases (CDK) and cyclins and up-regulating CDK-inhibitors.

机构信息

Department of Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843, USA.

出版信息

Reprod Toxicol. 2011 Jul;32(1):112-23. doi: 10.1016/j.reprotox.2011.05.007. Epub 2011 May 20.

Environmental contamination with hexavalent chromium (CrVI) has been increasing in the drinking water of the USA and developing countries. CrVI causes various health problems including menstrual disorders and infertility. Recently, we reported that CrVI causes granulosa cell apoptosis through the intrinsic apoptotic pathway. Our previous studies showed that postnatal exposure to CrVI arrests follicle development. In order to explore the underlying mechanism, primary and immortalized granulosa cells from rats were treated with 10 μM potassium dichromate and analyses of the cell cycle, and cell cycle regulatory proteins were performed. CrVI decreased cell proliferation as a result of cell cycle arrest and down-regulated cyclin-dependent kinases (CDK), cyclins, and PCNA while up-regulating CDK-inhibitors and down-regulating FSH receptor and ERβ. Vitamin C mitigated the effects of CrVI. This study shows that CrVI causes cell cycle arrest in granulosa cells by altering cell cycle regulatory proteins with potential intervention by vitamin C.

美国和发展中国家饮用水中六价铬（CrVI）的污染不断增加。CrVI 会导致各种健康问题，包括月经失调和不孕。最近，我们报道 CrVI 通过内在凋亡途径导致颗粒细胞凋亡。我们之前的研究表明，产后暴露于 CrVI 会阻止卵泡发育。为了探索潜在的机制，用 10μM 重铬酸钾处理大鼠原代和永生化颗粒细胞，并进行细胞周期分析和细胞周期调控蛋白分析。CrVI 通过细胞周期阻滞降低细胞增殖，并下调细胞周期依赖性激酶（CDK）、细胞周期蛋白和 PCNA，同时上调 CDK 抑制剂，下调 FSH 受体和 ERβ。维生素 C 减轻了 CrVI 的作用。本研究表明，CrVI 通过改变细胞周期调控蛋白导致颗粒细胞周期停滞，维生素 C 可能具有干预作用。