Retinoic acid and its geometrical isomers block both growth and fusion of L6 myoblasts by modulating the expression of protein kinase A.
All-trans retinoic acid (RA) and its geometrical isomers, such as 9-cis RA, 13-cis RA, and 9,13-di-cis RA, strongly inhibited both growth and fusion of L6 myoblasts. However, illumination of white light diminished their inhibitory activity on membrane fusion with little effect on cell growth. During myogenic differentiation, the intracellular level of cAMP decreased whereas the total activity of protein kinase A as well as the protein level of its regulatory subunit Ialpha (RIalpha) and catalytic subunit (Calpha) increased. RAs raised the intracellular level of cAMP by over 3-fold, but decreased the total activity of protein kinase A. Like RAs, dibutyryl-cAMP inhibited myoblast fusion and reduced the expression of both RIalpha and Calpha subunits. These results suggest that RAs negatively modulate the differentiation of L6 myoblasts by increasing the intracellular level of cAMP, which may in turn down-regulate the expression of protein kinase A and hence its activity.
Shin
Y J
YJ
Department of Biological Science, College of Natural Sciences, Ajou University, Suwon, Korea.
Woo
J H
JH
Chung
C H
CH
Kim
H S
HS
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D008027:Light; D008561:Membrane Fusion; D018482:Muscle, Skeletal / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D014212:Tretinoin / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology*
D014212:Tretinoin; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases