Inhibition of Hypoxia-induced Apoptosis in PC12 Cells by Estradiol.
- Author:
Ji Yeon JUNG
1
;
Kwang Hoon ROH
;
Yeon Jin JEONG
;
Sun Hun KIM
;
Eun Ju LEE
;
Min Seok KIM
;
Won Mann OH
;
Hee Kyun OH
;
Won Jae KIM
Author Information
1. Dental Science Research Institute, Department of Oral Physiology, School of Dentistry, Chonnam National University, Gwangju 500-757, Korea. wjkim@chonnam.ac.kr
- Publication Type:Original Article
- Keywords:
Estradiol;
Apoptosis;
CoCl2;
Caspase;
Bcl-2 family;
Mitochondria
- MeSH:
Animals;
Apoptosis*;
Caspase 8;
Caspases;
Cell Death;
Cell Survival;
Central Nervous System;
Cytochromes c;
Cytoplasm;
DNA Fragmentation;
Estradiol*;
Female;
Gene Expression;
Humans;
Mitochondria;
Neurons;
Neuroprotective Agents;
PC12 Cells*;
Reactive Oxygen Species;
Signal Transduction
- From:The Korean Journal of Physiology and Pharmacology
2005;9(4):231-238
- CountryRepublic of Korea
- Language:English
-
Abstract:
Neuronal apoptotic events, which result in cell death, are occurred in hypoxic/ischemic conditions. Estradiol is a female sex hormone with steroid structure known to provide neuroprotection through multiple mechanisms in the central nervous system. This study was aimed to investigate the signal transduction pathway of CoCl2-induced neuronal cell death and the inhibitory effects of estradiol. Administration of CoCl2 decreased cell viability in both a dose- and time-dependent manner in PC12 cells. CoCl2-induced cell death produced genomic DNA fragmentation and morphologic changes such as cell shrinkage and condensed nuclei. It was found that CoCl2-treated cells increased the reactive oxygen species (ROS) as well as caspase-8, -9 and -3 activities. However, pretreatment with estradiol before exposure to CoCl2 prevented the reduction in cell viability reduction and attenuated DNA fragmentation and morphologic changes caused by CoCl2. Furthermore, the CoCl2-induced increases of ROS levels and caspases activities were attenuated by estradiol. Gene expression analysis revealed that estradiol blocked the underexpression of the Bcl-2 and ameliorated the increase in the release of cytochrome c from mitochondria into cytoplasm and Fas-ligand (Fas-L) upregulated by CoCl2. These results suggest that CoCl2 induce apoptosis in PC12 cells through both mitochondria- and death receptor-mediated cell death pathway. Estradiol was found to have a neuroprotective effect against CoCl2-induced apoptosis through the inhibition of ROS production and by modulating apoptotic effectors associated with the mitochondria- and death-dependent pathway in PC12 cells.
