title: Extent of extracellular signal-regulated kinases phosphorylation determines the sensitivity of hepatic stellate cells to staurosporine-induced apoptosis.
abstract: OBJECTIVE
  Hepatic stellate cells (HSCs) are the principal cells responsible for the development of hepatic fibrosis and cirrhosis. During the fibrotic process, HSCs undergo proliferation and transdifferentiation from a quiescent to myofibroblast-like phenotype. The fate of myofibroblast like HSCs includes apoptosis or reversion back to a quiescent phenotype. The mechanisms involved in the apoptotic process of HSCs have yet to be determined. The purpose of the present study is to determine the effects of extracellular signal-regulated kinases (ERKs) phosphorylation on the apoptosis of HSCs induced by staurosporine.
  
  
  METHODS
  We used Western blot and flow cytometry to detect the expression level of ERK and cell apoptosis status in four rat hepatic stellate cell lines (CFSC-8B, -2G, -3H and-5H).
  
  
  RESULTS
  Each hepatic stellate cell line had a distinct morphology consistent with their expression level of α-SMA and that CFSC-8B cells had the highest α-SMA expression. Although all four cell types expressed similar levels of ERK1/2, phosphorylation levels were significantly higher in CFSC- 8B and CFSC-2G than in CFSC-3H and CFSC-5H cells. When CFSC-8B cells (high ERK1/2 phosphorylation) and CFSC-5H cells (low ERK1/2 phosphorylation) were employed to examine staurosporine-induced apoptosis, CFSC-8B cells were significantly more sensitive. Staurosporine further increased ERK1/2 phosphorylation in both cell lines.
  
  
  CONCLUSIONS
  ERK1/2 phosphorylation in HSCs determines the sensitivity of HSCs to staurosporine-induced apoptosis.
authors.affiliation: Faculty of Pharmacy, University of Manitoba, Winnipeg Manitoba R3E 0T5, Canada.
authors.forename: Jianghong
authors.initials: J
authors.lastname: Fan
authors.forename: Hong
authors.initials: H
authors.lastname: Shen
authors.forename: Qiaomei
authors.initials: Q
authors.lastname: Dai
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Burzynski
authors.forename: Gerald Y
authors.initials: GY
authors.lastname: Minuk
authors.forename: Yuewen
authors.initials: Y
authors.lastname: Gong
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005434:Flow Cytometry; D055166:Hepatic Stellate Cells / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology; D010766:Phosphorylation; D051381:Rats; D019311:Staurosporine / Q000494:pharmacology*
chemical_list: D048049:Extracellular Signal-Regulated MAP Kinases; D019311:Staurosporine