Hypothermia inhibits Fas-mediated apoptosis of primary mouse hepatocytes in culture

Tao Fu, Andres T. Blei, Noriaki Takamura, Tesu Lin, Danqing Guo, Honglin Li, Maurice R. O'Gorman, Humberto E. Soriano

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

Apoptosis occurs during the isolation and even short-term storage and culture of hepatocytes, and in the pathogenesis of liver diseases, such as hepatic failure and hepatitis. Therapeutic hypothermia has beneficial effects in experimental models of fulminant hepatic failure. The mechanisms underlying the potential benefits of mild hypothermia on the liver have not been well investigated. We examined the effects of temperature on soluble Fas ligand-induced apoptosis in freshly isolated mouse hepatocytes. Decreasing the culture temperature from 37°C to 32°C produced significant suppression of Fas-mediated apoptosis in cultured hepatocytes over a 12-h period. This observation was supported by cell morphology, flow cytometry analysis of cellular DNA content, and Annexin V-FITC staining of membrane phosphatidylserine translocation. In hypothermic conditions, Fas-mediated cytochrome c release from mitochondria of hepatocytes and the proximate downstream activation of caspase-9 were suppressed under mild hypothermic conditions. Effector caspase-7 activity was also inhibited at 32°C. In contrast, the activation of initiator caspase-8 and cleavage of Bid were not affected after Fas-ligand stimulation. These findings suggest that mild hypothermia suppresses Fas-mediated apoptosis of liver cells by the partial inhibition of signaling events including mitochondrial damage, cytochrome c release, and subsequent apoptosome formation and effector caspase activation.

Original languageEnglish (US)
Pages (from-to)667-676
Number of pages10
JournalCell Transplantation
Volume13
Issue number6
DOIs
StatePublished - Jan 1 2004
Externally publishedYes

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Keywords

  • Apoptosis
  • Caspases
  • Fas protein
  • Hepatocyte
  • Hypothermia

ASJC Scopus subject areas

  • Biomedical Engineering
  • Cell Biology
  • Transplantation

Cite this

Fu, T., Blei, A. T., Takamura, N., Lin, T., Guo, D., Li, H., O'Gorman, M. R., & Soriano, H. E. (2004). Hypothermia inhibits Fas-mediated apoptosis of primary mouse hepatocytes in culture. Cell Transplantation, 13(6), 667-676. https://doi.org/10.3727/000000004783983495