HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 286/5/H1801    most recent 00696.2003v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (9) Citing Articles via Google Scholar Google Scholar Articles by Payne, M. C. Articles by Fisher, S. A. Search for Related Content PubMed PubMed Citation Articles by Payne, M. C. Articles by Fisher, S. A.

Dynamic changes in expression of myosin phosphatase in a model of portal hypertension

¹Departments of Medicine and Physiology, Case Western Reserve School of Medicine, Cleveland, Ohio 44106; ²Department of Pharmacology, Physiology, and Therapeutics, University of North Dakota, Grand Forks, North Dakota 58202; and ³Department of Physiology, University of Massachusetts, Worcester, Massachusetts 01655

Submitted 21 July 2003 ; accepted in final form 22 December 2003

Myosin phosphatase is a target for signaling pathways that modulate calcium sensitivity of force production in smooth muscle. Myosin phosphatase targeting subunit 1 (MYPT1) isoforms are generated by cassette-type alternative splicing of exons in the central and 3' portion of the transcript. Exclusion of the 3' alternative exon, coding for the leucine zipper (LZ)-positive MYPT1 isoform, is associated with the ability to desensitize to calcium (relax) in response to NO/cGMP-dependent signaling. We examined expression of MYPT1 isoforms and smooth muscle phenotype in normal rat vessels and in a prehepatic model of portal hypertension characterized by arteriolar dilation. The large capacitance vessels, aorta, pulmonary artery, and inferior vena cava expressed predominantly the 3' exon-out/LZ-positive MYPT1 isoform. The first-order mesenteric resistance artery (MA1) and portal vein (PV) expressed severalfold higher levels of MYPT1 with predominance of the 3' exon-included/LZ-negative isoform. There was minor variation in the presence of the MYPT1 central alternative exons. Myosin heavy and light chain splice variants in part cosegregated with MYPT1 isoforms. In response to portal hypertension induced by PV ligature, abundance of MYPT1 in PV and MA1 was significantly reduced and switched to the LZ-positive isoform. These changes were evident within 1 day of PV ligature and were maintained for up to 10 days before reverting to control values at day 14. Alteration of MYPT1 expression was part of a complex change in protein expression that can be generalized as a modulation from a phasic (fast) to a tonic (slow) contractile phenotype. Implications of vascular smooth muscle phenotypic diversity and reversible phenotypic modulation in portal hypertension with regards to regulation of blood flow are discussed.

hypertrophy; phenotype; cGMP signaling

This article has been cited by other articles:

				Y. Gao, A. D. Portugal, J. Liu, S. Negash, W. Zhou, J. Tian, R. Xiang, L. D. Longo, and J. U. Raj Preservation of cGMP-induced relaxation of pulmonary veins of fetal lambs exposed to chronic high altitude hypoxia: role of PKG and Rho kinase Am J Physiol Lung Cell Mol Physiol, November 1, 2008; 295(5): L889 - L896. [Abstract] [Full Text] [PDF]

				S. Shukla and S. A. Fisher Tra2{beta} As a Novel Mediator of Vascular Smooth Muscle Diversification Circ. Res., August 29, 2008; 103(5): 485 - 492. [Abstract] [Full Text] [PDF]

				Y. Lu, H. Zhang, N. Gokina, M. Mandala, O. Sato, M. Ikebe, G. Osol, and S. A. Fisher Uterine artery myosin phosphatase isoform switching and increased sensitivity to SNP in a rat L-NAME model of hypertension of pregnancy Am J Physiol Cell Physiol, February 1, 2008; 294(2): C564 - C571. [Abstract] [Full Text] [PDF]

				H. Zhang and S. A. Fisher Conditioning Effect of Blood Flow on Resistance Artery Smooth Muscle Myosin Phosphatase Circ. Res., March 16, 2007; 100(5): 730 - 737. [Abstract] [Full Text] [PDF]

				P. G. Smith, A. Dreshaj, S. Chaudhuri, B. M. Onder, M. J. Mhanna, and R. J. Martin Hyperoxic conditions inhibit airway smooth muscle myosin phosphatase in rat pups Am J Physiol Lung Cell Mol Physiol, January 1, 2007; 292(1): L68 - L73. [Abstract] [Full Text] [PDF]

				S. SHUKLA, F. DEL GATTO-KONCZAK, R. BREATHNACH, and S. A. FISHER Competition of PTB with TIA proteins for binding to a U-rich cis-element determines tissue-specific splicing of the myosin phosphatase targeting subunit 1 RNA, November 1, 2005; 11(11): 1725 - 1736. [Abstract] [Full Text] [PDF]

				H.-Y. Zhang, Y. Shirasawa, X. Chen, H. Yu, and J. N. Benoit Impaired agonist-dependent myosin phosphorylation and decreased RhoA in rat portal hypertensive mesenteric vasculature Am J Physiol Gastrointest Liver Physiol, April 1, 2005; 288(4): G603 - G608. [Abstract] [Full Text] [PDF]