Heparin binding epidermal growth factor-like growth factor reduces ethanol-induced apoptosis and differentiation in human embryonic stem cells.
Alcohol affects approximately 1% (40,000) of new born infants each year and is the main preventable cause of mental retardation in the US. Ethanol alters cell signaling and promotes apoptosis and differentiation. Heparin-binding epidermal growth factor-like growth factor (HB-EGF), a member of the EGF family of growth factors, has been reported to prevent apoptosis and differentiation. We treated human embryonic stem cells (hESCs) with ethanol (20 mM) to reflect casual drinking, with and without HB-EGF to measure its ability to prevent ethanol-induced apoptosis and differentiation. Apoptosis was measured by DNA fragmentation (terminal dUTP nick-end labeling assays) and activated caspase-3, while differentiation was accessed by SSEA-1 and OCT-3/4; western blotting assessed MAPK signaling. HB-EGF reduced SSEA-1 and elevated OCT-3/4, while reducing the amount of activated caspase-3 and DNA fragmentation. Western blot analysis showed HB-EGF prevents ethanol from altering MAPK phosphorylation. This data suggests that ethanol-induced apoptosis was reduced by HB-EGF, while hESC pluripotency was maintained.
Nash
Rodney J
RJ
Department of Anesthesiology, Emory University School of Medicine, Atlanta, GA, 30322, USA. rjnash@emory.edu
Heimburg-Molinaro
Jamie
J
Nash
Rachel J
RJ
D017209:Apoptosis / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D053595:Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects*; D000431:Ethanol / Q000494:pharmacology*; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism* / Q000494:pharmacology
C587883:HBEGF protein, human; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D000431:Ethanol