Decreased myosin phosphatase target subunit 1(MYPT1) phosphorylation via attenuated rho kinase and zipper-interacting kinase activities in edematous intestinal smooth muscle
Article first published online: 11 JAN 2012
© 2012 Blackwell Publishing Ltd
Neurogastroenterology & Motility
Volume 24, Issue 3, pages 257–e109, March 2012
How to Cite
Chu, J., Miller, C. T., Kislitsyna, K., Laine, G. A., Stewart, R. H., Cox, C. S. and Uray, K. S. (2012), Decreased myosin phosphatase target subunit 1(MYPT1) phosphorylation via attenuated rho kinase and zipper-interacting kinase activities in edematous intestinal smooth muscle. Neurogastroenterology & Motility, 24: 257–e109. doi: 10.1111/j.1365-2982.2011.01855.x
- Issue published online: 8 FEB 2012
- Article first published online: 11 JAN 2012
- Received: 8 September 2011 Accepted for publication: 11 December 2011
- intestinal motility;
- intestinal smooth muscle;
- myosin light chain;
- rho kinase
Background Intestinal edema development after trauma resuscitation inhibits intestinal motility which results in ileus, preventing enteral feeding and compromising patient outcome. We have shown previously that decreased intestinal motility is associated with decreased smooth muscle myosin light chain (MLC) phosphorylation. The purpose of the present study was to investigate the mechanism of edema-induced decreases in MLC in a rodent model of intestinal edema.
Methods Intestinal edema was induced by a combination of resuscitation fluid administration and mesenteric venous hypertension. Sham operated animals served as controls. Contractile activity and alterations in the regulation of MLC including the regulation of MLC kinase (MLCK) and MLC phosphatase (MLCP) were measured.
Key Results Contraction amplitude and basal tone were significantly decreased in edematous intestinal smooth muscle compared with non-edematous tissue. Calcium sensitivity was also decreased in edematous tissue compared with non-edematous intestinal smooth muscle. Although inhibition of MLCK decreased contractile activity significantly less in edematous tissue compared with non-edematous tissue, MLCK activity in tissue lysates was not significantly different. Phosphorylation of MYPT was significantly lower in edematous tissue compared with non-edematous tissue. In addition, activities of both rho kinase and zipper-interacting kinase were significantly lower in edematous tissue.
Conclusions & Inferences We conclude from these data that interstitial intestinal edema inhibits MLC phosphorylation predominantly by decreasing inhibitory phosphorylation of the MLC targeting subunit (MYPT1) of MLC phosphatase via decreased ROCK and ZIPK activities, resulting in more MLC phosphatase activity.