Ferrostatins Inhibit Oxidative Lipid Damage and Cell Death in Diverse Disease Models

Skouta, Rachid; Dixon, Scott J.; Wang, Jianlin; Dunn, Denise; Orman, Marina; Shimada, Kenichi; Rosenberg, Paul A.; Lo, Donald C.; Weinberg, Joel M.; Linkermann, Andreas; Stockwell, Brent R.

doi:10.1021/ja411006a

articleJournal of the American Chemical SocietyMar 5, 2014HYBRID OA

Ferrostatins Inhibit Oxidative Lipid Damage and Cell Death in Diverse Disease Models

RSRachid Skouta SJScott J. Dixon JWJianlin Wang DDDenise Dunn MOMarina Orman

Northwest University · Columbia University · +7 more institutions

PubMed

Indexed incrossrefpubmed

Abstract

Ferrostatin-1 (Fer-1) inhibits ferroptosis, a form of regulated, oxidative, nonapoptotic cell death. We found that Fer-1 inhibited cell death in cellular models of Huntington's disease (HD), periventricular leukomalacia (PVL), and kidney dysfunction; Fer-1 inhibited lipid peroxidation, but not mitochondrial reactive oxygen species formation or lysosomal membrane permeability. We developed a mechanistic model to explain the activity of Fer-1, which guided the development of ferrostatins with improved properties. These studies suggest numerous therapeutic uses for ferrostatins, and that lipid peroxidation mediates diverse disease phenotypes.

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1,105

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FWCI: 14.80
Percentile: 100%
References: 44

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Topics & keywords

Topics

Keywords

Lipid peroxidation
Chemistry
Programmed cell death
Reactive oxygen species
Oxidative stress
Oxidative damage
Mitochondrion
Cell

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