Staurosporine aglycone bilaterally regulates ERK1/2 phosphorylation in rat pulmonary arterial smooth muscle cells.
Staurosporine, a protein kinase C (PKC) inhibitor, has been reported to regulate the phosphorylation of ERK1/2 in several cell lines. It is still unknown, however, whether its derivative staurosporine aglycone (SA) has the same effect on ERK1/2 activation. In this study, we investigated the effect of SA on ERK1/2 activity in rat pulmonary arteries and pulmonary arterial smooth muscle cells (PASMCs). The pulmonary arteries and PASMCs were treated with SA at different time points and concentrations, and the activation of ERK1/2 was analyzed by Western blotting. The results showed that SA at nanomolar concentrations suppressed ERK1/2 phosphorylation through the PKC pathway alone, but SA at 30 micromol/L for 2 h enhanced the phosphorylation of ERK1/2. The activation of ERK1/2 was inhibited by the MAPK/ERK kinase inhibitor PD98059 or the protein kinase A (PKA) activator isoproterenol. Together, these results suggest that SA has a strong dual regulating effect on ERK1/2 through the PKC and (or) PKA pathways in rat PASMCs.
Zhang
Jianing
J
Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University, Heilongjiang, PR China.
Tang
Xiaobo
X
Lu
Changlian
C
Guo
Lei
L
Zhang
Shuang
S
Chu
Xiaojie
X
Zhu
Daling
D
D000818:Animals; D015153:Blotting, Western; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000201:enzymology*; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D011651:Pulmonary Artery / Q000201:enzymology* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D019311:Staurosporine / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
D004791:Enzyme Inhibitors; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D048049:Extracellular Signal-Regulated MAP Kinases; D019311:Staurosporine