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ROLE OF GLUCOSE‐6‐PHOSPHATE DEHYDROGENASE IN PULMONARY VASCULAR REMODELING
Author(s) -
Chettimada Sukrutha,
Gupte Rakhee,
Gupte Sachin
Publication year - 2011
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.25.1_supplement.827.3
We have shown that rat pulmonary artery smooth muscle cells (PASMC) exposed to hypoxia (3% O 2 ) increased Glucose‐6‐phosphate dehydrogenase (G6PD) protein and activity. Here, we have investigated the effect of hypoxia on G6PD protein stability and its influence on PASMC proliferation. Lactacystin (10uM) treated PASMC significantly decreased G6PD degradation by ubiquitin‐proteasome pathway in normoxia. Next, we investigated the effect of elevated G6PD levels on cell proliferation in hypoxia. Inhibition of G6PD activity by 6‐aminonicotinamide (6AN, 1 mM) or dehydroepiandrosterone (DHEA, 100uM) decreased (0.6 to 0.15 fold) the S‐phase cells that was increased by hypoxia as compared to normoxia. Consistently, down‐regulation of G6PD expression (with siRNA) also decreased cell number. Furthermore, studies have demonstrated that elevated levels of CD133 + cells account for abnormal cell proliferation and genesis of vascular lesions. Interestingly, G6PD exhibited similar localization pattern as CD133 + cells in the perivascular regions of rat lungs exposed to 5 wks hypobaric hypoxia (10% O2), indicating that G6PD may be involved in infiltration of CD133 + stem cells in the lungs during hypoxia. This suggests that G6PD is a pO 2 sensitive protein and may control PASMC/stem cell proliferation and growth thereby contributing to PA remodeling in PAH. NIH grant: R01HL085352.