title: Regulation and the Mechanism of Estrogen on Cav1.2 Gene in Rat-Cultured Cortical Astrocytes.
abstract: L-type calcium channel (LTCC) gene Cav1.2 is believed to play an important role in the alteration of Ca(2+) homeostasis in brain astrocytes. Increasing evidence shows that alteration of intracellular Ca(2+) concentration is related to the effect of 17β-estradiol (E2) in a variety of neurophysiological and neuropathological conditions. In this study, we measured immunoreactivity of Cav1.2 protein expression in rat primary cortical astrocytes by using Western blots. We demonstrated that E2 upregulated Cav1.2 expression in a dose- and time-dependent manner and the effect of E2 on Cav1.2 expression were blocked by an estrogen receptor (ER) antagonist, ICI-182,780. The ER subtype-selective ERα agonists propylpyrazole triole (PPT) and ERβ agonist diarylpropionitrile (DPN) both increase the expression of Cav1.2 in a dose-dependent manner. Also, the PPT most closely mimicked the upregulation of Cav1.2 protein expression by E2. Similar experiments of 10 nM E2-treated ERα- or ERβ-knockdown astrocytes have also shown that the E2 regulation of Cav1.2 protein expression is mediated through an ERα-dependent pathway. Furthermore, we established that E2 did not change the level of Cav1.2 mRNA. The induction of E2-mediated Cav1.2 expression was inhibited by cycloheximide (CHX) but not by actinomycin D (Act-D), suggesting that E2 regulation of Cav1.2 expression occurred at a posttranscriptional level. We also found that E2 may increase Cav1.2 levels by decreasing its ubiquitination and degradation rate. These findings provide new information about the effect of E2 on Cav1.2 in astrocytes, particularly necessary for the treatment of neurological disease.
authors: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, 1 Youyi Road, Chongqing, 400016, China.|Department of Neurology, The People's Hospital of QianNan, Duyun, Guizhou, 558000, China.
authors: Ling
authors: L
authors: He
authors: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, 1 Youyi Road, Chongqing, 400016, China.
authors: Xiao-Tong
authors: XT
authors: Hu
authors: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, 1 Youyi Road, Chongqing, 400016, China.
authors: Yu-Jie
authors: YJ
authors: Lai
authors: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, 1 Youyi Road, Chongqing, 400016, China.
authors: Yan
authors: Y
authors: Long
authors: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, 1 Youyi Road, Chongqing, 400016, China.
authors: Lu
authors: L
authors: Liu
authors: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, 1 Youyi Road, Chongqing, 400016, China.
authors: Bing-Lin
authors: BL
authors: Zhu
authors: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, 1 Youyi Road, Chongqing, 400016, China. woodchen2015@163.com.
authors: Guo-Jun
authors: GJ
authors: Chen
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology* / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D059748:Proteolysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination; D015854:Up-Regulation
chemical_list: D020746:Calcium Channels, L-Type; D011960:Receptors, Estrogen; D004958:Estradiol
keywords: 17β-estradiol; Astrocyte; Cav1.2; Estrogen receptor