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:

Pulmonary Circulation

Dev K.Singh¹ 

关键词: hypoxia-induced pulmonary hypertension;    signal transduction;    cGMP;    pulmonary vasoconstriction;   

DOI  :  10.4103/2045-8932.93548

学科分类：医学（综合）

来源: Sage Journals

【 摘 要 】

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.

【 授权许可】

CC BY