The Korean Journal of Physiology and Pharmacology

  • 제9권4호
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  • Pages.231-238
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  • 2005
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  • 1226-4512(pISSN)
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  • 2093-3827(eISSN)
대한약리학회 (The Korean Society of Pharmacology)
권호 표지

Inhibition of Hypoxia-induced Apoptosis in PC12 Cells by Estradiol

  • Jung, Ji-Yeon (Dental Science Research institute, Department of Oral Physiology, School of Dentistry, Chonnam National University) ;
  • Roh, Kwang-Hoon (Dental Science Research institute, Department of Oral Physiology, School of Dentistry, Chonnam National University) ;
  • Jeong, Yeon-Jin (Dental Science Research institute, Department of Oral Physiology, School of Dentistry, Chonnam National University) ;
  • Kim, Sun-Hun (Dental Science Research institute, Department of Oral Physiology, School of Dentistry, Chonnam National University) ;
  • Lee, Eun-Ju (Dental Science Research institute, Department of Oral Physiology, School of Dentistry, Chonnam National University) ;
  • Kim, Min-Seok (Dental Science Research institute, Department of Oral Physiology, School of Dentistry, Chonnam National University) ;
  • Oh, Won-Mann (Dental Science Research institute, Department of Oral Physiology, School of Dentistry, Chonnam National University) ;
  • Oh, Hee-Kyun (Dental Science Research institute, Department of Oral Physiology, School of Dentistry, Chonnam National University) ;
  • Kim, Won-Jae (Dental Science Research institute, Department of Oral Physiology, School of Dentistry, Chonnam National University)
  • 발행 : 2005.08.21
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초록

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 $CoCl_2$-induced neuronal cell death and the inhibitory effects of estradiol. Administration of $CoCl_2$ decreased cell viability in both a dose- and time-dependent manner in PC12 cells. $CoCl_2$-induced cell death produced genomic DNA fragmentation and morphologic changes such as cell shrinkage and condensed nuclei. It was found that $CoCl_2$-treated cells increased the reactive oxygen species (ROS) as well as caspase-8, -9 and -3 activities. However, pretreatment with estradiol before exposure to $CoCl_2$ prevented the reduction in cell viability reduction and attenuated DNA fragmentation and morphologic changes caused by $CoCl_2$. Furthermore, the $CoCl_2$-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 $CoCl_2$. These results suggest that $CoCl_2$ induce apoptosis in PC12 cells through both mitochondria- and death receptor-mediated cell death pathway. Estradiol was found to have a neuroprotective effect against $CoCl_2$-induced apoptosis through the inhibition of ROS production and by modulating apoptotic effectors associated with the mitochondria- and death-dependent pathway in PC12 cells.

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