We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Inhibitory Effect of a Glutamine Antagonist on Proliferation and Migration of VSMCs via Simultaneous Attenuation of Glycolysis and Oxidative Phosphorylation.
- Authors
Park, Hyeon Young; Kim, Mi-Jin; Lee, Seunghyeong; Jin, Jonghwa; Lee, Sungwoo; Kim, Jung-Guk; Choi, Yeon-Kyung; Park, Keun-Gyu
- Abstract
Excessive proliferation and migration of vascular smooth muscle cells (VSMCs) contribute to the development of atherosclerosis and restenosis. Glycolysis and glutaminolysis are increased in rapidly proliferating VSMCs to support their increased energy requirements and biomass production. Thus, it is essential to develop new pharmacological tools that regulate metabolic reprogramming in VSMCs for treatment of atherosclerosis. The effects of 6-diazo-5-oxo-L-norleucine (DON), a glutamine antagonist, have been broadly investigated in highly proliferative cells; however, it is unclear whether DON inhibits proliferation of VSMCs and neointima formation. Here, we investigated the effects of DON on neointima formation in vivo as well as proliferation and migration of VSMCs in vitro. DON simultaneously inhibited FBS- or PDGF-stimulated glycolysis and glutaminolysis as well as mammalian target of rapamycin complex I activity in growth factor-stimulated VSMCs, and thereby suppressed their proliferation and migration. Furthermore, a DON-derived prodrug, named JHU-083, significantly attenuated carotid artery ligation-induced neointima formation in mice. Our results suggest that treatment with a glutamine antagonist is a promising approach to prevent progression of atherosclerosis and restenosis.
- Subjects
GLUTAMINE; OXIDATIVE phosphorylation; VASCULAR smooth muscle; GLYCOLYSIS; BIOMASS energy; BIOMASS production
- Publication
International Journal of Molecular Sciences, 2021, Vol 22, Issue 11, p5602
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms22115602