Inhibitors of cholera toxin-induced adenosine diphosphate ribosylation of
membrane-associated proteins block stem cell differentiation
TM Dexter, AD Whetton and CM Heyworth
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.
Volume 65,
Issue 6,
pp. 1544-1548,
06/01/1985
Copyright © 1985 by The American Society of Hematology