ACCUMULATION OF CYCLIC ADP-RIBOSE MEASURED BY A SPECIFIC RADIOIMMUNOASSAY IN DIFFERENTIATED HUMAN LEUKEMIC HL-60 CELLS WITH ALL-TRANS-RETINOIC ACID

Cyclic adenosine diphosphoribose (cADPR) is a novel candidate for the mediator of Ca2+ release from intracellular Ca2+ stores, The formation of this cyclic nucleotide is catalyzed by not only Aplysia ADP-ribosy l cyclase but also an ecto-form enzyme of NAD(+) glycohydrolase (NADas e), which was previously identified as all-trans-retinoic acid (RA)-in ducible CD38 in human leukemic HL-60 cells, In the present study, we d eveloped a radioimmunoassay specific for cADPR, by which more than 100 fmol of cADPR could be detected without any interference by other nuc leotides. The possible involvement of CD38 in, the formation of cellul ar cADPR was investigated with the radioimmunoassay method, A marked i ncrease in cellular cADPR was accompanied by all-trans-RA-induced diff erentiation of HL-60 cells, Moreover, a high level of cellular cADPR w as observed in other leukemic cell lines, in which CD38 mRNA was expre ssed, Thus, CD38, which was initially identified as an NADase, appeare d to be responsible for the formation of cellular cADPR.