Putative involvement of protein kinase C in proliferation of human myeloid progenitor cells.
The effects of two different potent inhibitors of protein kinase C, 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7) and staurosporine on human myeloid (CFU-C) and late erythroid progenitor cells (CFU-E) were studied using an in vitro clonal assay. Our objective was to determine whether protein kinase C has a role in signal transduction related to proliferation of these committed progenitor cells. The presence of H-7 or staurosporine led to an inhibition of colony formation stimulated by crude colony-stimulating factor (CSF), interleukin-3 (IL-3), granulocyte-macrophage CSF (GM-CSF), granulocyte CSF (G-CSF), or macrophage CSF (M-CSF) in a dose-dependent manner. N-(2-guanidinoethyl)-5-isoquinolinesulfonamide (HA-1004), a weaker analog of H-7, did not inhibit proliferation of CFU-C. Neither H-7 nor staurosporine had any effect on CFU-E formation. H-7 and staurosporine dose-dependently inhibited the protein kinase C from K562 cells. The potential of these compounds to inhibit proliferation of CFU-C correlated well with the magnitude of their inhibition of protein kinase C from K562 cells. The inhibition of proliferation of CFU-C appears to relate to the potential of these compounds to inhibit protein kinase C. Thus, activation of protein kinase C is presumably involved in the proliferation of CFU-C, and the regulatory system of CFU-E appears to differ from that of CFU-C.
Second Department of Internal Medicine, Mie University School of Medicine, Japan.
N
N
Katayama
M
M
Nishikawa
N
N
Minami
S
S
Shirakawa
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000328:Adult; D000470:Alkaloids; D001853:Bone Marrow / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D002999:Clone Cells / Q000187:drug effects; D003114:Colony-Forming Units Assay; D003115:Colony-Stimulating Factors / Q000494:pharmacology; D006131:Growth Inhibitors; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D007546:Isoquinolines; D004915:Leukemia, Erythroblastic, Acute / Q000201:enzymology; D010879:Piperazines; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D019311:Staurosporine; D013449:Sulfonamides
D000470:Alkaloids; D003115:Colony-Stimulating Factors; D006131:Growth Inhibitors; D007546:Isoquinolines; D010879:Piperazines; D013449:Sulfonamides; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C043204:N-(2-guanidinoethyl)-5-isoquinolinesulfonamide; D011493:Protein Kinase C; D019311:Staurosporine