TB4 inhibits mitochondrial C release, caspases; promotes Bcl-2
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Thymosin-beta4 inhibits corneal epithelial cell apoptosis after
ethanol exposure in vitro.
Sosne G, Siddiqi A, Kurpakus-Wheater M.
Department of Anatomy and Cell Biology, Kresge Eye Institute, Wayne
State University School of Medicine, Detroit, Michigan 48201, USA.
PURPOSE: The purpose of this study was to determine the effect of
thymosin beta 4 (Tbeta(4)) treatment on human corneal epithelial cells
exposed to ethanol in vitro. The efficacy of Tbeta(4) in preventing
mitochondrial disruption and in inhibiting caspase-mediated apoptosis
was examined. METHODS: Nontransformed human corneal epithelial cells
(HCECs) at passage 4 were untreated or treated with ethanol (20% for 20
seconds) or a combination of ethanol and Tbeta(4). The cells were
allowed to recover from ethanol treatment for 24 hours. Mitochondrial
membrane integrity and the release of cytochrome c to the cytoplasm were
assessed using microscopy, Western blot, and ELISA. Bcl-2 expression and
cell proliferation were measured using ELISA. Colorimetric activity
assays were completed for caspase-2, -3, -8, and -9. RESULTS: Tbeta(4)
treatment decreased deleterious mitochondrial alterations, significantly
decreased cytochrome c release from mitochondria, and increased Bcl-2
expression in ethanol-exposed human corneal epithelial cells. In
ethanol-exposed corneal epithelium Tbeta(4) treatment inhibited
caspase-2, -3, -8, and -9 activity, with caspase-8 showing the most
significant inhibition. Tbeta(4) treatment resulted in no significant
effect on the proliferation of human corneal epithelial cells after
ethanol exposure. CONCLUSIONS: Tbeta(4) plays an antiapoptotic role
under conditions of epithelial cell challenge with an external stress
such as exposure to ethanol. Tbeta(4) may function as an antiapoptotic
agent by inhibiting the release of cytochrome c from mitochondria and by
suppressing the activation of caspases.
PMID: 15037574 [PubMed - indexed for MEDLINE]