Open AccessHypoxia Modulates the Expression of Leucine Zipper‐Positive MYPT1 and its Interaction with Protein Kinase G and Rho Kinases in Pulmonary Arterial Smooth Muscle Cells
Author(s) -
Singh Dev K.,
Sarkar Joy,
Raghavan Aarti,
Reddy Sekhar P.,
Raj J. Usha
Publication year - 2011
Publication title -
pulmonary circulation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.791
H-Index - 40
ISSN - 2045-8940
DOI - 10.4103/2045-8932.93548
Subject(s) - myosin light chain phosphatase , rhoa , rho associated protein kinase , rock2 , hypoxia (environmental) , rock1 , microbiology and biotechnology , myosin light chain kinase , protein kinase a , gene knockdown , medicine , phosphorylation , biology , signal transduction , chemistry , biochemistry , gene , oxygen , organic chemistry
We have shown previously that acute hypoxia downregulates protein kinase G (PKG) expression and activity in ovine fetal pulmonary vessels and pulmonary arterial smooth muscle cells (SMC). Here, we report that acute hypoxia also reduces the expression of leucinezipper‐positive MYPT1 (LZ + MYPT1), a subunit of myosin light chain (MLC) phosphatase, in ovine fetal pulmonary arterial SMC. We found that in hypoxia, there is greater interaction between LZ + MYPT1 and RhoA and Rho kinase 1 (ROCK1)/Rho kinase 2 (ROCK2) and decreased interaction between LZ + MYPT1 and PKG, resulting in increased MLC 20 phosphorylation, a higher pMLC 20 /MLC 20 ratio and SMC contraction. In normoxic SMC PKG overexpression, LZ + MYPT1 expression is upregulated while PKG knockdown had an opposite effect. LZ + MYPT1 overexpression enhanced the interaction between PKG and LZ + MYPT1. Overexpression of a mutant LZ − MYPT1 isoform in SMC mimicked the effects of acute hypoxia and decreased pMLC 20 /MLC 20 ratio. Collectively, our data suggest that hypoxia downregulates LZ + MYPT1 expression by suppressing PKG levels, reduces the interaction of LZ + MYPT1 with PKG and promotes LZ + MYPT1 interaction with RhoA or ROCK1/ROCK2, thereby promoting pulmonary arterial SMC contraction.