Multicellular organisms undergo a variety of predetermined and precisely controlled programmed cell deaths during development, such as apoptosis, necroptosis, pyroptosis, and ferroptosis.
Ferroptosis is a novel iron-dependent programmed cell death discovered by Brent Stockwell's lab at Columbia University in 2012, which is induced by excessive accumulation of peroxidized lipids, and its morphological features, mode of action, and molecular mechanisms are very different from those of other programmed deaths. Also, there are multiple defense pathways against iron death in the cell, the most prominent one being mediated by glutathione peroxidase 4 (GPX4), which inhibits the onset of iron death by glutathione (GSH)-specific catalysis of peroxidized lipids.
On November 8, 2023, Brent Stockwell's team published in the Cell subjournal Cell Chemical Biology a The study was published in the Cell journal Cell Chemical Biology.
The study found that iron death is the driving event of iron-overload-mediated injury in both in vitro cellular experiments and in vivo animal models. In contrast, exogenously added oleic acid protected cells and tissues from iron-overload-mediated injury by inhibiting iron death.
Ferroptosis is a novel iron-dependent programmed cell death discovered by Brent Stockwell's lab at Columbia University in 2012, which is induced by excessive accumulation of peroxidized lipids, and its morphological features, mode of action, and molecular mechanisms are very different from those of other programmed deaths. Also, there are multiple defense pathways against iron death in the cell, the most prominent one being mediated by glutathione peroxidase 4 (GPX4), which inhibits the onset of iron death by glutathione (GSH)-specific catalysis of peroxidized lipids.
On November 8, 2023, Brent Stockwell's team published in the Cell subjournal Cell Chemical Biology a The study was published in the Cell journal Cell Chemical Biology.
The study found that iron death is the driving event of iron-overload-mediated injury in both in vitro cellular experiments and in vivo animal models. In contrast, exogenously added oleic acid protected cells and tissues from iron-overload-mediated injury by inhibiting iron death.
These results suggest that it is feasible to reduce iron overload-mediated injury through therapeutic and nutritional strategies that inhibit iron death, and that the addition of oleic acid to the diet may represent a novel approach to the treatment of iron overload disease.
Iron overload is an important disease type characterized by accumulation of iron in tissues that induces multi-organ toxicity leading to iron death in kidney, liver, and neuronal cell lines, but we do not yet fully understand its mechanisms.
In this latest study, the team found that iron death occurs in the context of iron overload-mediated injury through the use of cell lines, cryptic nematodes of Hidradenitis elegans, and mouse models. Exogenous oleic acid protects cultured cells and nematodes in vitro from the toxicity of iron overload by inhibiting iron death. And in mice, oleic acid protected their livers from iron overload-induced hepatic lipid peroxidation and injury.
Oleic acid altered cellular lipid composition, which was characterized by reduced levels of the polyunsaturated fatty acid acyl phospholipids and reduced levels of ether-linked phospholipids. The protective effect of oleic acid in cells was attenuated by GW6471, a PPAR-α antagonist, as well as by nematodes lacking the nuclear hormone receptor NHR-49, a functional homologue of PPAR-α.
These results emphasize that iron death is a driver of iron overload-mediated injury, and that iron overload-mediated injury can be inhibited by oleic acid. Oleic acid, a monounsaturated fatty acid, represents a potential therapeutic approach that holds promise for mitigating organ damage in patients with iron overload.
In this latest study, the team found that iron death occurs in the context of iron overload-mediated injury through the use of cell lines, cryptic nematodes of Hidradenitis elegans, and mouse models. Exogenous oleic acid protects cultured cells and nematodes in vitro from the toxicity of iron overload by inhibiting iron death. And in mice, oleic acid protected their livers from iron overload-induced hepatic lipid peroxidation and injury.
Oleic acid altered cellular lipid composition, which was characterized by reduced levels of the polyunsaturated fatty acid acyl phospholipids and reduced levels of ether-linked phospholipids. The protective effect of oleic acid in cells was attenuated by GW6471, a PPAR-α antagonist, as well as by nematodes lacking the nuclear hormone receptor NHR-49, a functional homologue of PPAR-α.
These results emphasize that iron death is a driver of iron overload-mediated injury, and that iron overload-mediated injury can be inhibited by oleic acid. Oleic acid, a monounsaturated fatty acid, represents a potential therapeutic approach that holds promise for mitigating organ damage in patients with iron overload.
