What question did this study set out to answer?

To evaluate how hepatitis C virus proteins influence Fas-mediated apoptotic signaling and liver cell survival in vivo.

April 1, 2001Journal of Biological ChemistryOpen Access

Inhibition of Cytochrome c Release in Fas-mediated Signaling Pathway in Transgenic Mice Induced to Express Hepatitis C Viral Proteins

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Authors

KMKeigo MachidaUniversity of Southern California KTKyoko Tsukiyama–KoharaKagoshima University ESEiji SeikeSakakibara Hospital

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Implication

Transgenic mouse study reveals suppression of Fas-mediated liver cell death by hepatitis C viral proteins, suggesting a mechanism for persistent viral infection.

Key Points

To evaluate how hepatitis C virus proteins influence Fas-mediated apoptotic signaling and liver cell survival in vivo.
Generated transgenic mice expressing hepatitis C virus core, E1, E2, and NS2 proteins regulated via a Cre/loxP switching system.
Administered Fas-stimulating antibodies to analyze mouse lethality, histopathological changes, and hepatic DNA fragmentation.
Assayed mitochondrial cytochrome c release and the activation states of caspase-8, caspase-9, and caspase-3/7 in hepatic tissues.
HCV protein expression conferred marked resistance to Fas antibody-induced lethality and significantly reduced apoptotic liver cell death and DNA fragmentation.
Mitochondrial release of cytochrome c was blocked, leading to downstream inhibition of caspase-9 and caspase-3/7 activation, while upstream caspase-8 activity remained unaffected.

Cite This Study

Machida et al. (2001) studied this question.

synapsesocial.com/papers/6a9fb8f4164081e7bed55723 https://doi.org/10.1074/jbc.m010137200

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Implication

Transgenic mouse study reveals suppression of Fas-mediated liver cell death by hepatitis C viral proteins, suggesting a mechanism for persistent viral infection.

Inhibition of Cytochrome c Release in Fas-mediated Signaling Pathway in Transgenic Mice Induced to Express Hepatitis C Viral Proteins

Discussion

Member takes

Implication

Key Points

Cite This Study

Inhibition of Cytochrome c Release in Fas-mediated Signaling Pathway in Transgenic Mice Induced to Express Hepatitis C Viral Proteins

Discussion

Member takes

Implication

Key Points

Cite This Study

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