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        Overexpression of Ornithine Decarboxylase Suppresses Thapsigargin-Induced Apoptosis

        Hsieh, Wei-Chung,Hsu, Pei-Chen,Liao, Ya-Fan,Young, Shu-Ting,Wang, Zeng-Wei,Lin, Chih-Li,Tsay, Gregory J.,Lee, Huei,Hung, Hui-Chih,Liu, Guang-Yaw Korean Society for Molecular and Cellular Biology 2010 Molecules and cells Vol.30 No.4

        Ornithine decarboxylase (ODC), the key enzyme of polyamine biosynthesis, has paradoxical roles in apoptosis. Our published papers show overexpression of ODC prevents the apoptosis induced by many cytotoxic drugs. Thapsigargin (TG) is an inhibitor of the sarcoplasmic/endoplasmic reticulum (ER) $Ca^{2+}$ ATPase (SERCA) pumps and causes ER stress-induced apoptosis. We used ODC overexpressing cell lines to examine whether overexpression of ODC inhibits TG-induced apoptosis. Our results indicated overexpression of ODC attenuated TG-induced apoptosis. Overexpression of ODC blocked procaspse-4 cleavage and phosphorylation of protein kinase-like ER-resident kinase (PERK), triggered by TG. It also attenuated the increase in CAAT/enhancer binding protein homologous protein (CHOP). Cells with overexpressed ODC had greater Bcl-2 expression. Overexpression of ODC preserved the expression of Bcl-2, inhibited the increase in Bak and stabilized mitochondrial membrane potential without the influences of TG. Cytochrome c release and downstream caspase activation were blocked. That is, overexpression of ODC inhibits the mitochondria-mediated apoptotic pathway, induced by TG. Finally, overexpression of ODC maintains the protein and mRNA expression of SERCA. In conclusion, overexpression of ODC suppresses TG-induced apoptosis by blocking caspase-4 activation and PERK phosphorylation, attenuating CHOP expression and inhibiting the mitochondria-mediated apoptotic pathway.

      • KCI등재

        Overexpression of Ornithine Decarboxylase Suppresses Thapsigargin-Induced Apoptosis

        Wei-Chung Hsieh,Pei-Chen Hsu,Ya-Fan Liao,Shu-Ting Young,Zeng-Wei Wang,Chih-Li Lin,Gregory J. Tsay,Huei Lee,Hui-Chih Hung,Guang-Yaw Liu 한국분자세포생물학회 2010 Molecules and cells Vol.30 No.4

        Ornithine decarboxylase (ODC), the key enzyme of poly-amine biosynthesis, has paradoxical roles in apoptosis. Our published papers show overexpression of ODC pre-vents the apoptosis induced by many cytotoxic drugs. Thapsigargin (TG) is an inhibitor of the sarcoplasmic/en-doplasmic reticulum (ER) Ca2+ ATPase (SERCA) pumps and causes ER stress-induced apoptosis. We used ODC overexpressing cell lines to examine whether overexpres-sion of ODC inhibits TG-induced apoptosis. Our results indicated overexpression of ODC attenuated TG-induced apoptosis. Overexpression of ODC blocked procaspse-4 cleavage and phosphorylation of protein kinase-like ER-resident kinase (PERK), triggered by TG. It also attenuated the increase in CAAT/enhancer binding protein homolo-gous protein (CHOP). Cells with overexpressed ODC had greater Bcl-2 expression. Overexpression of ODC pre-served the expression of Bcl-2, inhibited the increase in Bak and stabilized mitochondrial membrane potential without the influences of TG. Cytochrome c release and downstream caspase activation were blocked. That is, overexpression of ODC inhibits the mitochondria-medi-ated apoptotic pathway, induced by TG. Finally, overex-pression of ODC maintains the protein and mRNA expres-sion of SERCA. In conclusion, overexpression of ODC suppresses TG-induced apoptosis by blocking caspase-4 activation and PERK phosphorylation, attenuating CHOP expression and inhibiting the mitochondria-mediated apoptotic pathway.

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