Inhibitors of cholera toxin-induced adenosine diphosphate ribosylation of membrane-associated proteins block stem cell differentiation.
Two potent inhibitors of mono-adenosine diphosphate (ADP) ribosylation have recently been described and characterized, named p-methoxylbenzylaminodecamethylene guanidine sulfate (MBAMG) and benzylaminododecylguanine hydrochloride (BADGH). We have used these agents to investigate the role of ADP ribosylation in hematopoiesis using long-term marrow cultures. The addition of MBAMG (10(-6) mol/L) or BADGH (5 X 10(-4) mol/L) led to both an inhibition of mature cell production and the development of colony-stimulating factor (CSF-1)-responsive GM-CFC, but had no effect upon spleen colony-forming units (CFU-S) or on progenitor cells which respond to the multilineage stimulating factor present in WEHI-3B cell-conditioned medium. These data indicate that these inhibitors of mono-ADP ribosylation can block the commitment and/or differentiation of stem cells and infers that ADP ribosylation may be of some importance in the hematopoietic process.
D000246:Adenosine Diphosphate Ribose / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D001854:Bone Marrow Cells; D002454:Cell Differentiation / Q000187:drug effects*; D002772:Cholera Toxin / Q000494:pharmacology*; D046508:Culture Techniques; D005260:Female; D006146:Guanidines / Q000494:pharmacology; D006147:Guanine / Q000031:analogs & derivatives / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D009702:Nucleoside Diphosphate Sugars / Q000037:antagonists & inhibitors*
D006146:Guanidines; D008565:Membrane Proteins; D009702:Nucleoside Diphosphate Sugars; D000246:Adenosine Diphosphate Ribose; D006147:Guanine; D002772:Cholera Toxin; C045661:4-methoxybenzylaminodecamethylene guanidine; C045662:benzylaminododecylguanine