ArticleAmerican journal of physiology. Cell physiology2009
A rapid, PPAR-gamma-dependent effect of pioglitazone on the phosphorylation of MYPT.
Article in American journal of physiology. Cell physiology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12 citing papers in PubMed, 32 citations in OpenAlex.
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- Inhibition of neutrophil extracellular trap formation alleviates vascular dysfunction in type 1 diabetic mice.Science advances · 2023Article
- The Synergistic Enhancement of Cloning Efficiency in Individualized Human Pluripotent Stem Cells by Peroxisome Proliferative-activated Receptor-γ (PPARγ) Activation and Rho-associated Kinase (ROCK) Inhibition.The Journal of biological chemistry · 2015Article
- High salt diet modulates vascular response in A2AAR (+/+) and A 2AAR (-/-) mice: role of sEH, PPARγ, and K ATP channels.Molecular and cellular biochemistry · 2015Article
- Identification of protein kinase C activation as a novel mechanism for RGS2 protein upregulation through phenotypic screening of natural product extracts.Molecular pharmacology · 2014Article
- Endothelin-1 decreases endothelial PPARγ signaling and impairs angiogenesis after chronic intrauterine pulmonary hypertension.American journal of physiology. Lung cellular and molecular physiology · 2014Article
- Peroxisome proliferator activated receptor-γ-Rho-kinase interactions contribute to vascular remodeling after chronic intrauterine pulmonary hypertension.American journal of physiology. Lung cellular and molecular physiology · 2014Article
- The prognostic values of leukocyte Rho kinase activity in acute ischemic stroke.BioMed research international · 2014Article
- Cardiotonic steroids stabilize regulator of G protein signaling 2 protein levels.Molecular pharmacology · 2012Article
- Potential drug mechanism(s) targeting the contractile status of hepatic stellate cells.Frontiers in pharmacology · 2012Article
- Serine496 of β2 subunit of L-type Ca2+ channel participates in molecular crosstalk between activation of (Na++K+)-ATPase and the channel.Biochemical and biophysical research communications · 2010Article
- Does peroxisome proliferator-activated receptor-gamma (PPAR gamma) protect from hypertension directly through effects in the vasculature?The Journal of biological chemistry · 2010Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Peroxisome proliferator-activated receptor (PPAR)-gamma ligands, thiazolidinediones, have been demonstrated to regulate vascular reactivity. We examined the effect of pioglitazone (PIO; 20 muM) in rat primary cultured aortic smooth muscle cells on constitutive phosphorylation of the regulatory subunit of myosin phosphatase (MYPT). PIO decreased the phosphorylation of Thr(697) on MYPT within 15 min, and the inhibition was maintained up to 6 h. The PPAR-gamma antagonist GW-9662 (5 microM) abrogated the inhibition of Thr(697) phosphorylation mediated by PIO. Because longer-term PIO treatment inhibits RhoA/Rho kinase (ROCK) signaling and Thr(697) phosphorylation, we tested the effect of the ROCK inhibitor Y-27632 (10 muM) on the inhibition of Thr(697) phosphorylation by PIO. Y-27632 alone inhibited Thr(697) phosphorylation, and there was an additive effect with PIO. In addition, up to 1 h of PIO treatment did not affect RhoA localization or decrease ROCK-dependent phosphorylation of Thr(855). These results suggest that the effect of PIO is independent of inhibition of RhoA/ROCK. PIO increased the phosphorylation of Ser(696) in the same time course as its effect on Thr(697). Ser(696) has been shown to be phosphorylated by PKA and PKG. PKA inhibitor H-89 (10 microM) and PKG inhibitor KT-5823 (0.5 microM) abrogated the effect of PIO on both Thr(697) and Ser(696) phosphorylation. The constitutive turnover of phosphorylation of Thr(697) is rapid, suggesting that the decreased phosphorylation of Thr(697) by PIO is due to enhanced phosphorylation of Ser(696). This is supported by the finding that PIO blocks ANG II-stimulated phosphorylation of Thr(697) but not ANG II-stimulated RhoA translocation. Therefore, the effect of shorter-term PIO apparently is to increase myosin light chain phosphatase activity, thereby desensitizing the vascular smooth muscle to agonist signaling.
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