Glutaminase-1 stimulates the proliferation, migration, and survival of human endothelial cells.

Biochemical Pharmacology
Kelly J PeytonWilliam Durante

Abstract

Glutaminase-1 (GLS1) is a mitochondrial enzyme found in endothelial cells (ECs) that metabolizes glutamine to glutamate and ammonia. Although glutaminolysis modulates the function of human umbilical vein ECs, it is not known whether these findings extend to human ECs beyond the fetal circulation. Furthermore, the molecular mechanism by which GLS1 regulates EC function is not defined. In this study, we show that the absence of glutamine in the culture media or the inhibition of GLS1 activity or expression blocked the proliferation and migration of ECs derived from the human umbilical vein, the human aorta, and the human microvasculature. GLS1 inhibition arrested ECs in the G0/G1 phase of the cell cycle and this was associated with a significant decline in cyclin A expression. Restoration of cyclin A expression via adenoviral-mediated gene transfer improved the proliferative, but not the migratory, response of GLS1-inhibited ECs. Glutamine deprivation or GLS1 inhibition also stimulated the production of reactive oxygen species and this was associated with a marked decline in heme oxygenase-1 (HO-1) expression. GLS1 inhibition also sensitized ECs to the cytotoxic effect of hydrogen peroxide and this was prevented by the overexpres...Continue Reading

Citations

Jan 11, 2020·Frontiers in Physiology·Jacopo SabbatinelliAngelica Giuliani
May 7, 2019·Frontiers in Pharmacology·Ghazaleh BehnammaneshWilliam Durante
Jul 9, 2020·Frontiers in Pharmacology·Camila Benavides-RivasPatricio A Castro
Oct 21, 2020·Journal of Clinical Medicine·Céline A SchoonjansBernard Gallez
Apr 27, 2021·Antioxidants & Redox Signaling·Masuko Ushio-FukaiTohru Fukai
Apr 27, 2021·Metabolism: Clinical and Experimental·Yimin ShenHong Ma
Jun 15, 2021·Frontiers in Neuroscience·Eduard YakubovHans-Herbert Steiner
Aug 28, 2021·International Journal of Molecular Sciences·William DuranteKelly J Peyton
Sep 2, 2021·JACC. Basic to Translational Science·Anja KarlstaedtBonnie Ky
Oct 27, 2021·Cancer Biology & Therapy·Vinod S BishtKiran Ambatipudi
Dec 21, 2021·ACS Pharmacology & Translational Science·Renna K E CostaSandra M G Dias

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