title: SM22alpha is required for agonist-induced regulation of contractility: evidence from SM22alpha knockout mice.
abstract: The present study was undertaken to determine whether SM22alpha participates in the regulation of vascular smooth muscle contractility using SM22alpha knockout mice and, if so, to investigate the mechanisms involved. Aortic ring preparations were mounted and equilibrated in organ baths for 60 min before observing contractile responses to 50 mM KCl, and then exposed to contractile agents such as phenylephrine and phorbol ester. Measurement of isometric contractions using a computerized data acquisition system was combined with molecular or cellular experiments. Interestingly, the aortas from SM22alpha-deficient mice (SM22(-/-LacZ)) displayed an almost three-fold increase in the level of SM22beta protein compared to wild-type mice, but no change in the levels of caldesmon, actin, desmin or calponin. Ca2+-independent contraction in response to phenylephrine or phorbol ester was significantly decreased in the SM22alpha-deficient mice, whereas in the presence of Ca2+ neither contraction nor subcellular translocation of myosin light chain kinase (MLCK) in response to phenylephrine or 50 mM KCl was significantly affected. A decrease in phosphorylation of extracellular signal regulated kinase (ERK) 1/2 was observed in the SM22alpha-deficient mice and this may be related to the decreased vascular contractility. Taken together, this study provides evidence for a pivotal role of SM22alpha in the regulation of Ca2+-independent vascular contractility.
authors.affiliation: Department of Pharmacology, College of Pharmacy, Catholic University of Daegu, Gyeongsan 712-702, Korea.
authors.forename: Hyun Dong
authors.initials: HD
authors.lastname: Je
authors.forename: Uy Dong
authors.initials: UD
authors.lastname: Sohn
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001013:Aorta, Thoracic / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002148:Calmodulin-Binding Proteins / Q000378:metabolism; D003893:Desmin / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D066298:In Vitro Techniques; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009119:Muscle Contraction; D009124:Muscle Proteins / Q000235:genetics / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009219:Myosin-Light-Chain Kinase / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology; D010703:Phorbol Esters / Q000494:pharmacology; D010766:Phosphorylation; D011189:Potassium Chloride / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D000096985:Calponins
chemical_list: D000199:Actins; D002118:Calcium; D002135:Calcium-Binding Proteins; D002148:Calmodulin-Binding Proteins; D003893:Desmin; D048049:Extracellular Signal-Regulated MAP Kinases; D008840:Microfilament Proteins; D009124:Muscle Proteins; D009219:Myosin-Light-Chain Kinase; D010656:Phenylephrine; D010703:Phorbol Esters; D011189:Potassium Chloride; D020033:Protein Isoforms; D014662:Vasoconstrictor Agents; D000096985:Calponins; C051615:transgelin; C029705:12-deoxyphorbolphenylacetate-20-acetate