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Glucose‐6‐phosphate dehydrogenase regulates pulmonary artery smooth muscle cell phenotype
Author(s) -
chettimada sukrutha,
Gupte Rakhee,
Gupte Sachin
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.873.9
Subject(s) - downregulation and upregulation , cell growth , pentose phosphate pathway , cell cycle , flow cytometry , chemistry , vascular smooth muscle , myocardin , apoptosis , cell , endocrinology , cancer research , microbiology and biotechnology , medicine , biology , enzyme , biochemistry , glycolysis , smooth muscle , gene expression , serum response factor , gene
Hyperplasia and hypertrophy of pulmonary artery smooth muscle cells (PASMCs) are thought to be the leading cause of medial thickening, which obliterate vascular lumen and increase pressure via contributing to hypoxic vascular remodeling. We have previously shown that glucose‐6‐phosphate dehydrogenase (G6PD), the first enzyme of pentose phosphate pathway (PPP), is activated in PASMCs exposed to chronic hypoxia (CH; 72 hrs; 3% O 2 ). In previous studies, we found that the cell numbers determined by CyQuant cell proliferation assay increased by CH. In current study, cell‐proliferation and ‐cycle determined by BrdU assay and flow cytometry, respectively, demonstrate that CH increased both the number of cells in S‐Phase and cell proliferation. Inhibition of G6PD with dehydroepiandrosterone/6‐ aminonicotinamide/siRNA suppressed this increase. Furthermore, we demonstrate that CH evokes de‐differentiation of PASMCs via downregulation of myocardin and SM22α (80% and 31.5% vs. normoxia ), and upregulation of cyclin A and phospho‐histoneH3 (87.3% and 243% vs. normoxia), an S and G2M phase protein, respectively. Intriguingly, G6PD inhibition was able to suppress the de‐differentiation by re‐expressing myocardin and downregulating cyclin D1 and phospho‐histoneH3 expression to normal level. In conclusion, G6PD derived NADPH or the PPP metabolites plays a significant role in regulating PASMCs phenotype.