G6PD activity contributes to the regulation of histone acetylation and gene expression in smooth muscle cells and to the pathogenesis of vascular diseases.

G6PD activity contributes to the regulation of histone acetylation and gene expression in smooth muscle cells and to the pathogenesis of vascular diseases. Am J Physiol Heart Circ Physiol. 2021 Jan 08;: Authors: Dhagia V, Kitagawa A, Jacob C, Zheng C, D'Alessandro A, Edwards JG, Rocic P, Gupte R, Gupte SA Abstract We aimed to determine: 1) the mechanism(s) that enable glucose-6-phosphate dehydrogenase (G6PD) to regulate serum response factor (SRF)- and myocardin (MYOCD)‑driven smooth muscle cell (SMC)-restricted gene expression, a process that aids in the differentiation of SMCs; and 2) whether G6PD-mediated metabolic reprogramming contributes to the pathogenesis of vascular diseases in metabolic syndrome (MetS). Inhibition of G6PD activity increased (>30%) expression of SMC-restricted genes and concurrently decreased (40%) the growth of human and rat SMCs ex vivo. Expression of SMC-restricted genes decreased (>100-fold) across successive passages in primary cultures of SMCs isolated from mouse aorta. G6PD inhibition increased Myh11 (47%) while decreasing (>50%) Sca-1, a stem cell marker, in cells passaged seven times. Similarly, CRISPR-Cas9-mediated expression of the loss-of-function Mediterranean variant of G6PD (S188F; G6PDS188F) in rats promoted transcription of SMC‑restricted genes. G6PD knockdown or inhibition decreased (48.5%) HDAC activity, enriched (by 3-fold) H3K27ac on the Myocd promoter, and increased Myocd a...
Source: American Journal of Physiology. Heart and Circulatory Physiology - Category: Physiology Authors: Tags: Am J Physiol Heart Circ Physiol Source Type: research