Taher M M
Division of Cardiology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298, USA.
Biochem Mol Biol Int. 1996 May;39(2):267-77. doi: 10.1080/15216549600201281.
It has been observed that in growth arrested vascular smooth muscle cells herbimycin A treatment completely inhibits the activation of mitogen activated protein kinase induced by phorbol 12-myristate 13-acetate (a phorbol ester). Since herbimycin A is a tyrosine kinase inhibitor, this finding raised the possibility of protein kinase C inhibition or down regulation by this compound. Herbimycin A significantly inhibited phorbol myristate acetate-mediated protein kinase C activation as measured by in situ glycogen synthase (GS) peptide and neurogranin peptide phosphorylation in vascular smooth muscle cells. Basal protein kinase activity, i.e. kinase activity without phorbol ester treatment to vascular smooth muscle cells, was also decreased by the treatment of herbimycin A. These findings suggest that herbimycin A also inhibits protein kinase C in vascular smooth muscle cells.
据观察,在生长停滞的血管平滑肌细胞中,除莠霉素A处理可完全抑制佛波醇12 -肉豆蔻酸酯13 -乙酸酯(一种佛波酯)诱导的丝裂原活化蛋白激酶的激活。由于除莠霉素A是一种酪氨酸激酶抑制剂,这一发现增加了该化合物抑制或下调蛋白激酶C的可能性。通过血管平滑肌细胞中糖原合酶(GS)肽和神经颗粒蛋白肽的原位磷酸化测定,除莠霉素A显著抑制佛波醇肉豆蔻酸酯乙酸酯介导的蛋白激酶C活化。用除莠霉素A处理也可降低基础蛋白激酶活性,即未用佛波酯处理血管平滑肌细胞时的激酶活性。这些发现表明,除莠霉素A也可抑制血管平滑肌细胞中的蛋白激酶C。