Glc-6-PD and PKG contribute to hypoxia-induced decrease in smooth muscle cell contractile phenotype proteins in pulmonary artery.

American Journal of Physiology. Lung Cellular and Molecular Physiology
Sukrutha ChettimadaSachin A Gupte

Abstract

Persistent hypoxic pulmonary vasoconstriction (HPV) plays a significant role in the pathogenesis of pulmonary hypertension, which is an emerging clinical problem around the world. We recently showed that hypoxia-induced activation of glucose-6-phosphate dehydrogenase (Glc-6-PD) in pulmonary artery smooth muscle links metabolic changes within smooth muscle cells to HPV and that inhibition of Glc-6PD reduces acute HPV. Here, we demonstrate that exposing pulmonary arterial rings to hypoxia (20-30 Torr) for 12 h in vitro significantly (P < 0.05) reduces (by 30-50%) SM22α and smooth muscle myosin heavy chain expression and evokes HPV. Glc-6-PD activity was also elevated in hypoxic pulmonary arteries. Inhibition of Glc-6-PD activity prevented the hypoxia-induced reduction in SM22α expression and inhibited HPV by 80-90% (P < 0.05). Furthermore, Glc-6-PD and protein kinase G (PKG) formed a complex in pulmonary artery, and Glc-6-PD inhibition increased PKG-mediated phosphorylation of VASP (p-VASP). In turn, increasing PKG activity upregulated SM22α expression and attenuated HPV evoked by Glc-6-PD inhibition. Increasing passive tension (from 0.8 to 3.0 g) in hypoxic arteries for 12 h reduced Glc-6-PD, increased p-VASP and SM22α levels, a...Continue Reading

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Citations

Dec 3, 2014·Matrix Biology : Journal of the International Society for Matrix Biology·Olga V SazonovaMatthew A Nugent
Jan 10, 2018·Annals of the Rheumatic Diseases·Alexandru-Emil MateiJörg H W Distler
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Nov 3, 2016·American Journal of Physiology. Lung Cellular and Molecular Physiology·John C HuetschLarissa A Shimoda
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Aug 8, 2019·American Journal of Physiology. Lung Cellular and Molecular Physiology·Hang YuMichael S Wolin
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Mar 20, 2021·European Journal of Pharmacology·Peter J MoroneJoyce Cheung-Flynn
Mar 25, 2021·The Journal of Pharmacology and Experimental Therapeutics·Atsushi KitagawaSachin A Gupte

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