Promotion of fas-mediated apoptosis in type II cells by high doses of hepatocyte growth factor bypasses the mitochondrial requirement

Yongge Zhao, Daniell Difrancesca, Xue Wang, Reza Zarnegar, George K. Michalopoulos, Xiao-Ming Yin

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

The death receptor pathway is coupled to the mitochondria apoptosis pathway. However, mitochondrial participation, which is stimulated by Bid but suppressed by Bcl-2/Bcl-xL, is required in certain cells (Type II), but not in others (Type I). While these differences were originally characterized in the lymphoid cell lines, the typical Type II cells are represented by hepatocytes in vivo. The molecular mechanisms that distinguish Type II from Type I cells and the regulation are not fully understood. Fas can be sequestered by the HGF receptor c-Met and high doses of HGF can promote cell death by freeing Fas from c-Met complex. We thus reasoned that treatment of the Type II cells with high doses of HGF could enhance Fas-mediated apoptosis and spare the mitochondria amplification. Indeed, such treatment led to increased apoptosis in Type II lymphoid cells, which could not be blocked by Bcl-x L. Moreover, significant hepatocyte apoptosis was induced by this scheme in the absence of Bid with increased dissociation of Fas from c-Met. These findings indicate that high doses of HGF could be used to promote apoptosis in Type II cells bypassing the requirement for mitochondria activation.

Original languageEnglish (US)
Pages (from-to)556-563
Number of pages8
JournalJournal of Cellular Physiology
Volume213
Issue number2
DOIs
StatePublished - Nov 2007
Externally publishedYes

Fingerprint

Hepatocyte Growth Factor
Mitochondria
Apoptosis
Hepatocytes
Lymphocytes
Proto-Oncogene Proteins c-met
Death Domain Receptors
Cell death
Amplification
Cell Death
Chemical activation
Cells
Cell Line

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

Promotion of fas-mediated apoptosis in type II cells by high doses of hepatocyte growth factor bypasses the mitochondrial requirement. / Zhao, Yongge; Difrancesca, Daniell; Wang, Xue; Zarnegar, Reza; Michalopoulos, George K.; Yin, Xiao-Ming.

In: Journal of Cellular Physiology, Vol. 213, No. 2, 11.2007, p. 556-563.

Research output: Contribution to journalArticle

Zhao, Yongge ; Difrancesca, Daniell ; Wang, Xue ; Zarnegar, Reza ; Michalopoulos, George K. ; Yin, Xiao-Ming. / Promotion of fas-mediated apoptosis in type II cells by high doses of hepatocyte growth factor bypasses the mitochondrial requirement. In: Journal of Cellular Physiology. 2007 ; Vol. 213, No. 2. pp. 556-563.
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