tailieunhanh - Báo cáo khoa học: Enhancement of oxidative stress-induced apoptosis by Hsp105a in mouse embryonal F9 cells

Hsp105aisoneof themajormammalianheat shockproteins that belongs to the HSP105/110 family, and is expressed at especially high levels in the brain as compared with other tissues in mammals. Previously, we showed that Hsp105a prevents stress-induced apoptosis in neuronal PC12 cells, and is a novel anti-apoptotic neuroprotective factor in the mammalian brain. | Eur. J. Biochem. 269 4143-4151 2002 FEBS 2002 doi Enhancement of oxidative stress-induced apoptosis by Hsp105a in mouse embryonal F9 cells Nobuyuki Yamagishi Youhei Saito Keiichi Ishihara and Takumi Hatayama Department of Biochemistry Kyoto Pharmaceutical University Japan Hsp105a is one of the major mammalian heat shock proteins that belongs to the HSP105 110 family and is expressed at especially high levels in the brain as compared with other tissues in mammals. Previously we showed that Hsp105a prevents stress-induced apoptosis in neuronal PC12 cells and is a novel anti-apoptotic neuroprotective factor in the mammalian brain. On the other hand we have also demonstrated that Hsp105a is expressed transiently at high levels during mouse embryogenesis and is found not only in various tissues but also in apoptotic cells. In the present study to elucidate the role of Hsp105a during mouse embryogenesis we established mouse embryonal F9 cell lines that constitutively over-express Hsp105a. Overexpression of Hsp105a enhanced hydrogen peroxide induced apoptosis by enhancing the activation of caspase-3 poly ADP-ribose polymerase cleavage cytochrome c release and activation of p38 mitogen-activated protein kinase p38 . Furthermore oxidative stress-induced apoptosis was suppressed by SB202190 a potent inhibitor of p38 in F9 cells. These findings indicated that the activation of p38 is an essential step for apoptosis in F9 cells and that Hsp105a enhances activation of p38 release of cytochrome c and caspase activation. Hsp105a may play important roles in organogenesis during which marked apoptosis occurs by enhancing apoptosis during mouse embryogenesis. Keywords apoptosis F9 cells Hsp105 p38 MAPK oxidative stress. Cell death is classified into two major morphologically and biochemically distinct modes necrosis and apoptosis 1 . Necrosis is characterized by swelling of organelles and cells followed by lysis of the plasma membrane and random DNA

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