Miyamoto K, Nakamura S, Ikeda K, Nomura M, Wakusawa S, Hidaka H
Research Laboratory for Development of Medicine, School of Pharmacy, Hokuriku University, Kanazawa, Japan.
Biochem Pharmacol. 1993 Feb 9;45(3):772-5. doi: 10.1016/0006-2952(93)90155-p.
The effects of protein kinase inhibitors on the proliferation of A65 murine leukemia cells were studied. The proliferation of phorbol ester-dependent A65 cells was inhibited by N-(2-methylpiperazyl)-5-isoquinolinesulfonamide (H-7), a protein kinase C inhibitor, at a significantly lower concentration than the phorbol ester-independent variant, while both cell types had the same sensitivity to N-[2-[N-[3-(4-chlorophenyl)-1-methyl-2-propenyl]amino]ethyl]-5- isoquinolinesulfonamide, a selective inhibitor of protein kinase A, and staurosporine, a non-selective inhibitor of protein kinases. When the effect of H-7 on the cell cycle was analysed by flow-cytometry, the agent at concentrations that completely inhibited the cell proliferation significantly increased the proportion in the G0/G1 phase of both cell types but decreased that in the S phase, without much change in the G2/M phase. These results suggest that H-7 blocks the G1/S transition by inhibiting protein kinase C, whether the proliferation is dependent on phorbol ester or not.
研究了蛋白激酶抑制剂对A65小鼠白血病细胞增殖的影响。蛋白激酶C抑制剂N-(2-甲基哌嗪基)-5-异喹啉磺酰胺（H-7）抑制佛波酯依赖性A65细胞的增殖时，所需浓度显著低于佛波酯非依赖性变体，而两种细胞类型对蛋白激酶A的选择性抑制剂N-[2-[N-[3-(4-氯苯基)-1-甲基-2-丙烯基]氨基]乙基]-5-异喹啉磺酰胺和蛋白激酶的非选择性抑制剂星形孢菌素具有相同的敏感性。当通过流式细胞术分析H-7对细胞周期的影响时，完全抑制细胞增殖的浓度的该试剂显著增加了两种细胞类型在G0/G1期的比例，但降低了S期的比例，而G2/M期变化不大。这些结果表明，无论增殖是否依赖佛波酯，H-7都通过抑制蛋白激酶C来阻断G1/S转换。
