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Inhibition of tumor necrosis factor‐induced apoptosis in transgenic mouse liver expressing creatine kinase
Author(s) -
Hatano Etsuro,
Tanaka Akira,
Kanazawa Akiyoshi,
Tsuyuki Shigeru,
Tsunekawa Shoji,
Iwata Shingo,
Takahashi Rei,
Chance Britton,
Yamaoka Yoshio
Publication year - 2004
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/j.1478-3231.2004.0939.x
Subject(s) - apoptosis , genetically modified mouse , transgene , tumor necrosis factor alpha , phosphocreatine , biology , medicine , endocrinology , necrosis , mitochondrion , creatine kinase , caspase , microbiology and biotechnology , programmed cell death , biochemistry , gene , energy metabolism
Abstract: Background: The mitochondrion acts as a pivotal decision center in many types of apoptotic responses. To clarify the effects of the enhanced mitochondrial function on tumor necrosis factorα (TNFα)‐induced apoptosis, we studied hepatic injuries in transgenic mice whose livers express creatine kinase (CK). Methods: Mice fed a diet containing 10% creatine, came to accumulate phosphocreatine and to enhance hepatic ATP levels and mitochondrial oxidative phosphorylation activities. TNFα‐mediated hepatic apoptosis in normally fed and Cr‐feeding CK transgenic mice were assessed. Results: TNFα and actinomycin D cause severe liver failure in normally fed transgenic mice, and in the wild‐type mice. In contrast, no significant elevations in transaminase levels after injection were observed in Cr feeding transgenic mice. The disruption of the mitochondrial transmembrane potential at 2 h after TNFα injection, prior to ATP depletion, activation of caspase 3 like protease, and DNA fragmentation at 4–6 h after injection, were observed in normally fed transgenic mice. These were fully suppressed in Cr feeding transgenic mice. However, anti‐Fas antibody‐induced apoptosis was not inhibited in both groups. Conclusions: The results indicate that TNFα‐induced apoptosis was inhibited in CK transgenic mice livers by maintaining mitochondrial function.