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Signal Transduction in Smooth Muscle Selected Contribution : Insulin utilizes NO / cGMP pathway to activate myosin phosphatase via Rho inhibition in vascular smooth muscle
| Content Provider | Semantic Scholar |
|---|---|
| Author | Sandu, Oana Alexandra Ito, Masaaki Begum, Najma |
| Copyright Year | 2001 |
| Abstract | Sandu, Oana A., Masaaki Ito, and Najma Begum. Selected Contribution: Insulin utilizes NO/cGMP pathway to activate myosin phosphatase via Rho inhibition in vascular smooth muscle. J Appl Physiol 91: 1475–1482, 2001.—Our laboratory has recently demonstrated that insulin induces relaxation of vascular smooth muscle cells (VSMCs) by activating myosin-bound phosphatase (MBP) and by inhibiting Rho kinase (Begum N, Duddy N, Sandu OA, Reinzie J, and Ragolia L. Mol Endocrinol 14: 1365–1376, 2000). In this study, we tested the hypothesis that insulin via the nitric oxide (NO)/cGMP pathway may inactivate Rho, resulting in a decrease in phosphorylation of the myosin-bound subunit (MBSThr695) of MBP and in its activation. Treatment of confluent serum-starved VSMCs with insulin prevented thrombin-induced increases in membrane-associated RhoA, Rho kinase activation, and site-specific phosphorylation of MBSThr695 of MBP and caused MBP activation. Preexposure to NG-monomethyl-L-arginine, a NO synthase inhibitor, and R-p-8-(4-chlorophenylthio)cGMP, a cGMP antagonist, attenuated insulin’s inhibitory effect on Rho translocation and restored thrombin-mediated Rho kinase activation and sitespecific MBSThr695 phosphorylation, resulting in MBP inactivation. In contrast, 8-bromo-cGMP, a cGMP agonist, mimicked insulin’s inhibitory effects by abolishing thrombinmediated Rho signaling and promoted dephosphorylation of MBSThr695. Furthermore, expression of a dominant-negative RhoA decreased basal as well as thrombin-induced MBSThr695 phosphorylation and caused insulin activation of MBP. Collectively, these results indicate that insulin inhibits Rho signaling by decreasing RhoA translocation via the NO/cGMP signaling pathway to cause MBP activation via site-specific dephosphorylation of its regulatory subunit MBS. |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://jap.physiology.org/content/jap/91/3/1475.full.pdf |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
