Retinoid-Mediated Signaling Pathways in CD38 Antigen Expression in Myeloid Leukemia Cells

Abstract

The lymphocyte cell surface antigen CD38, which was originally described as a differentiation marker, has emerged as an important multifunctional protein. Its most intriguing and well characterized function is its ability to catalyze the synthesis of cyclic ADP-ribose (cADPR) from NAD. cADPR serves as an important second messenger in controlling the release of intracellular calcium from ryanodine-sensitive intracellular pools. By virtue of its ability to synthesize cADPR as well as to act as an adhesion and signal transduction molecule, CD38 may play a role in such diverse physiological processes as cell growth, apoptosis, differentiation, and inflammation. Equally interesting is the pattern of CD38 expression in hematopoietic cells. In the bone marrow, early precursor cells predominantly express CD38 antigen, whereas mature circulating blood cells lack or express very low levels. The expression is also high on malignant hematopoietic cells and thus may be of prognostic relevance in certain leukemias. Presently, there is little information available on the factors that regulate the expression of CD38 antigen in hematopoietic cells. In this review, we summarize recent findings on the regulation of CD38 antigen by retinoids (vitamin A and related compounds). At least in the myeloid cell lineage, retinoids appear to be exquisitely potent and specific inducers of CD38 antigen expression, and retinoid-induced expression of CD38 is mediated via activation of the retinoic acid-alpha (RAR alpha) nuclear receptor.

Early mitochondrial alterations in ATRA-induced cell death

“…Calcium is an important cellular second messenger, which can regulate cell proliferation, 26 mitochondrial function 27 as well as differentiation 28 and apoptosis. 29 In our experiments, we investigated mitochondrial functional parameters, such as respiration and calcium uptake capacity, as well as different apoptosis-associated parameters (involvement of Bax, loss of DC m , release of cytochrome c) in the presence and/or absence of the growth factor G-CSF.…”

Expression of retinoic acid receptor–target genes during retinoic acid therapy for acute promyelocytic leukemia

“…Interferonand interferon-a rapidly induce CD38 expression in mature tonsillar B cells and myeloid cells. 6 The plasma levels of these two cytokines did not change during ATRA therapy. Therefore, increased CD38 expression must have been caused by the effect of retinoic acid.…”

“…6 The function of CD38 is to catalyze the synthesis of cyclic ADP-ribose from nicotinamide adenine dinucleotide (NAD), and cyclic ADPribose acts as a mediator, or modulator, of intracellular calcium mobilization. 7 In addition to affecting this enzymatic activity, CD38 may also play a role in cell growth, apoptosis, differentiation, and inflammation.…”

“…6 MRP1 function was determined by calcein acetoxymethyl ester (calcein-AM) (Dojin Chem., Kumamoto, Japan) efflux and its inhibition by probenecid. 6 The accumulation (%) of Rh123 and the efflux (%) of calcein-AM were determined as reported previously. 6 The amount of mdr-1 and mrp-1 mRNA were determined by realtime PCR analysis.…”

“…6 The accumulation (%) of Rh123 and the efflux (%) of calcein-AM were determined as reported previously. 6 The amount of mdr-1 and mrp-1 mRNA were determined by realtime PCR analysis. The primer set to amplify mdr-1 and mrp-1…”