The Important Role of Caspase-10 in Sodium Butyrate-Induced Apoptosis

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概要

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• Butyrate, a short chain fatty acid, exhibits a wide variety of biological effects including theinhibition of cell growth, change of cellular morphology and the induction of apoptosis. Sodiumbutyrate-induced apoptosis has been reported to associate with the up-regulation ofpro-apoptotic Bax expression, and the down-regulation of anti-apoptotic Bcl-2 and Bcl-XLexpressions. However, in some cases, butyrate has also been shown to cause apoptosis withoutchange in Bcl-2, Bcl-XL and/or Bax. This study investigates the detailed mechanisms of sodiumbutyrate-induced apoptosis. The effect of sodium butyrate was analyzed in the induction ofcaspase activities, formation of caspase active forms and mRNA levels in human breast cancercell line MRK-nu-1. Induction of activities of caspase-3, -10 and, to some extent, -8 and formationof DNA fragmentation were observed with sodium butyrate in a dose- and/or time-dependentmanner. The levels of caspase-10 mRNA expression markedly increased in a time-dependentmanner by the treatment of sodium butyrate, whereas caspase-8 mRNA expression was notchanged. Inhibitors of caspase-8 and caspase-10 reduced caspase-3 activity and subsequent DNAfragmentation induced by sodium butyrate. These caspase inhibitors also inhibited the cleavageof pro-caspase-3 to the active forms indicated by Western blotting analysis. Pyrrolidinedithiocarbamate also inhibited the induction of caspase-10 mRNA expression and caspase-3activation. Contrary to other reports, levels of Bcl-2, Bcl-XL and Bax mRNA expressions werenot distinctly changed by even 5 mM sodium butyrate treatment. Our results suggest that sodiumbutyrate may trigger apoptosis via the induction of the caspase-10 expression.

• 神戸大学の論文

著者

• Yokoyama Yoshiko

  Departments Of Molecular Epidemiology Kobe University Graduate School Of Medicine

• Kano Kazutaka

  Departments Of Molecular Epidemiology Kobe University Graduate School Of Medicine

• Kano Kazutaka

  Department Of Physiological Chemistry And Nutrition Faculty Of Medicine University Of Tokyo

• Nohara Kazunari

  Departments of Molecular Epidemiology, and Public Health Kobe University Graduate School of Medicine

• Nohara Kazunari

  Departments Of Molecular Epidemiology And Public Health Kobe University Graduate School Of Medicine

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• The Important Role of Caspase-10 in Sodium Butyrate-Induced Apoptosis

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