EFFECTS OF GENISTEIN AND STAUROSPORINE ON ANGIOTENSIN-II-INDUCED DNA-SYNTHESIS, PROTEIN-SYNTHESIS AND MITOGEN-ACTIVATED PROTEIN-KINASE ACTIVATION IN VASCULAR SMOOTH-MUSCLE CELLS
M. Hanada et al., EFFECTS OF GENISTEIN AND STAUROSPORINE ON ANGIOTENSIN-II-INDUCED DNA-SYNTHESIS, PROTEIN-SYNTHESIS AND MITOGEN-ACTIVATED PROTEIN-KINASE ACTIVATION IN VASCULAR SMOOTH-MUSCLE CELLS, Biological & pharmaceutical bulletin, 21(10), 1998, pp. 1045-1049
This study examines the effects of protein kinase inhibitors and activ
ator on angiotensin II-induced DNA synthesis and protein synthesis of
rat aortic smooth muscle cells. In quiescent confluent cells, angioten
sin II induced a concentration-dependent increase in thymidine incorpo
ration and leucine incorporation. The tyrosine kinase inhibitor genist
ein caused an inhibition of the angiotensin II-induced DNA synthesis b
ut not of the agent-induced protein synthesis. The protein kinase C in
hibitors staurosporine and calphostin C caused an inhibition of the an
giotensin II-induced protein synthesis but not of the agent-induced DN
A synthesis. The protein kinase C activator phorbol 12-myristate 13-ac
etate stimulated protein synthesis. Angiotensin II stimulated mitogen-
activated protein (MAP) kinases and the angiotensin II-induced MAP kin
ase activation was inhibited by genistein but not by staurosporine. Th
ese findings suggest that angiotensin II-induced DNA synthesis is at l
east partly mediated via protein-tyrosine phosphorylation and angioten
sin II-induced protein synthesis is at least partly mediated by activa
tion of protein kinase C. It seems likely that MAP kinase activation i
s involved in DNA synthesis but not in protein synthesis induced by an
giotensin II.