Lipid peroxidation and the subsequent cell death transmitting from ferroptotic cells to neighboring cells

Abstract

Ferroptosis regulated cell death due to the iron-dependent accumulation of lipid peroxide. Ferroptosis is known to constitute the pathology of ischemic diseases, neurodegenerative diseases, and steatohepatitis and also works as a suppressing mechanism against cancer. However, how ferroptotic cells affect surrounding cells remains elusive. We herein report the transfer phenomenon of lipid peroxidation and cell death from ferroptotic cells to nearby cells that are not exposed to ferroptotic inducers (FINs). While primary mouse embryonic fibroblasts (MEFs) and NIH3T3 cells contained senescence-associated β-galactosidase (SA-β-gal)-positive cells, they were decreased upon induction of ferroptosis with FINs. The SA-β-gal decrease was inhibited by ferroptotic inhibitors and knockdown of Atg7, pointing to the involvement of lipid peroxidation and activated autophagosome formation during ferroptosis. A transfer of cell culture medium of cells treated with FINs, type 1 or 2, caused the reduction in SA-β-gal-positive cells in recipient cells that had not been exposed to FINs. Real-time imaging of Kusabira Orange-marked reporter MEFs cocultured with ferroptotic cells showed the generation of lipid peroxide and deaths of the reporter cells. These results indicate that lipid peroxidation and its aftereffects propagate from ferroptotic cells to surrounding cells, even when the surrounding cells are not exposed to FINs. Ferroptotic cells are not merely dying cells but also work as signal transmitters inducing a chain of further ferroptosis.

Vitamin K1 inhibits ferroptosis and counteracts a detrimental effect of phenprocoumon in experimental acute kidney injury

“…Benedikt Kolbrink and Friedrich Alexander von Samson-Himmelstjerna contributed equally to this work. nature [14,15], leading to pronounced kidney cell death and organ failure [3][4][5].…”

“…If these protective mechanisms are inactivated by pharmacological agents or in the context of pathological conditions, ferroptosis occurs, as is the case in AKI. Once activated, ferroptosis spreads to neighboring cells due to its propagative nature [ 14 , 15 ], leading to pronounced kidney cell death and organ failure [ 3 – 5 ].…”

miR-92b-3p Exerts Neuroprotective Effects on Ischemia/Reperfusion-Induced Cerebral Injury via Targeting NOX4 in a Rat Model

“…Ischemic stroke is mainly due to insufficient blood supply to the brain caused by cerebral artery occlusion, resulting in local cerebral tissue ischemia and hypoxia. Neuronal cells in the brain tissue exhibit energy or ion pump obstacles [ 4 – 6 ] and rapidly develop reversible or irreversible neuronal damage; therefore, subsequent reperfusion of acute ischemic stroke is essential for neuronal cell rescue [ 7 ]. However, experimental and clinical evidence has shown that restoration of perfusion, the contradiction of increased damage in the short term, often leads to reperfusion injury [ 8 – 14 ].…”

The Administration Effect of Lactic Acid Bacteria Reducing Environmental Alkyl and Fatty Acid Hydroperoxides on Piglets in the Absence of Antimicrobial Agents and in the Presence of Iron

“…In the research of probiotic lactic acid bacteria in pigs, there are some reports on the protective activity to oxidative stress [30,38], but there is no report referring to the effect of lactic acid bacteria on iron toxicity. Although at this stage the mechanism by which LpP1-2 suppresses iron toxicity is unknown, iron-dependent cell death (ferroptosis) has been reported to be involved in various human diseases [39][40][41]. In addition, the degradation of lipid peroxide [42] and the suppression of lipid peroxide toxicity [43][44] have been pointed out to be involved in the suppression of ferroptosis.…”