Possible involvement of protein kinase C in the aberrant regulation of erythropoiesis in polycythemia vera.
To examine the possible involvement of protein kinase C (PKC) in the regulation of aberrant erythropoiesis of polycythemia vera (PV), we investigated the effects of PKC inhibitors on in vitro burst-forming unit of erythroid (BFU-E)-derived colony formation by bone marrow (BM) and peripheral blood (PB) cells obtained from five PV patients. 1-(Isoquinoline-sulfonyl)-2-methylpiperazine dihydrochloride (H-7), an inhibitor of PKC, suppressed the colony formation by BM and PB cells of PV patients in a dose-dependent manner, similar to those in the normal individuals. However, the 50% inhibitory concentrations (IC50) of H-7 in PV BM and PB cells were significantly higher than those in normal BM and PB cells, respectively. The BFU-E-derived colony formation by PV BM and PB cells was also less affected by Staurosporine, another PKC inhibitor, than those in a normal subject. Furthermore, in the study of PV, the IC50 of endogenous colonies formed in the absence of erythropoietin was much higher than that of colonies formed by the stimulation of erythropoietin. By contrast, N-(2-guanidinoethyl)-5-isoquinolinesulfonamide dihydrochloride (HA1004), a cyclic AMP-dependent kinase inhibitor, did not have such inhibitory effects. These findings suggest that PKC, as a second messenger, is involved in the regulation of aberrant erythropoiesis of PV.
Kawada
E
E
Third Department of Internal Medicine, Gunma University School of Medicine, Maebashi, Japan.
Tamura
J
J
Kubota
K
K
Murakami
H
H
Naruse
T
T
Tsuchiya
J
J
D000328:Adult; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015672:Erythroid Precursor Cells / Q000187:drug effects; D004920:Erythropoiesis / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D011087:Polycythemia Vera / Q000097:blood* / Q000201:enzymology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000502:physiology*
D004791:Enzyme Inhibitors; D011493:Protein Kinase C