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Telokin expression and the effect of hypoxia on its phosphorylation status in smooth muscle cells from small and large pulmonary arteries. Am J Physiol Lung Cell Mol Physiol 2008 Jun;294(6):L1166-73

Date

04/01/2008

Pubmed ID

18375742

DOI

10.1152/ajplung.00375.2007

Abstract

Small pulmonary arteries (SPA), <500 microm diameter of the cat, constrict when exposed to hypoxia, whereas larger arteries (large pulmonary arteries; LPA), >800 microm diameter, show little or no response. It is unknown why different contractile responses occur within the same vascular bed, but activator or repressor proteins within the smooth muscle cell (SMC) can modify myosin phosphatase and myosin light chain kinase (MLCK), thereby influencing the phosphorylation state of myosin light chain (MLC) and ultimately, contraction. Telokin, a protein with a sequence identical to the COOH-terminal domain of MLCK, is expressed in smooth muscle where in its phosphorylated state it inhibits myosin phosphatase, binds to unphosphorylated myosin, and helps maintain smooth muscle relaxation. We measured telokin mRNA and telokin protein in smooth muscle from different diameter feline pulmonary arteries and sought to determine whether changes in the phosphorylation status of telokin and MLC occurred during hypoxia. In pulmonary arteries, telokin expression varied inversely with artery diameter, but cerebral arteries showed neither telokin protein nor telokin mRNA. Although telokin and MLC were distributed uniformly throughout the SPA muscle cell cytoplasm, they were not colocalized. During hypoxia, telokin dephosphorylated, and MLC became increasingly phosphorylated in SPA SMC, whereas in LPA SMC there was no change in either telokin or MLC phosphorylation. When LPA SMC were exposed to phenylephrine, MLC phosphorylation increased with no change in telokin phosphorylation. These results suggest that in SPA, phosphorylated telokin may help maintain relaxation under unstimulated conditions, whereas in LPA, telokin's function remains undetermined.

Author List

Madden JA, Dantuma MW, Sorokina EA, Weihrauch D, Kleinman JG

Author

Dorothee Weihrauch DVM, PhD Professor in the Anesthesiology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Cats
Cells, Cultured
Cerebral Arteries
Female
Gene Expression
Hypoxia
Male
Muscle, Smooth, Vascular
Myosin-Light-Chain Kinase
Peptide Fragments
Phosphorylation
Pulmonary Artery
RNA, Messenger
jenkins-FCD Prod-411 e00897e83867fcfa48419861683711f8d99adb75