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- Title
Hypoxia modulates the expression of leucine zipper-positive MYPT1 and its interaction with protein kinase G and Rho kinases in pulmonary arterial smooth muscle cells.
- Authors
Singh, Dev K.; Sarkar, Joy; Raghavan, Aarti; Reddy, Sekhar P.; Raj, J. Usha
- Abstract
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 MLC20 phosphorylation, a higher pMLC20/MLC20 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 pMLC20/MLC20 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.
- Subjects
HYPOXEMIA; LEUCINE; PROTEIN kinases; MUSCLE cells; MYOSIN light chain kinase
- Publication
Pulmonary Circulation, 2011, Vol 1, Issue 4, p487
- ISSN
2045-8932
- Publication type
Article
- DOI
10.4103/2045-8932.93548