Mitochondrion-targeted antioxidant SkQ1 prevents rapid animal death caused by highly diverse shocks.

Autor: Skulachev VP; Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russia, 119991. skulach@belozersky.msu.ru., Vyssokikh MY; Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russia, 119991. mikhail.vyssokikh@gmail.com., Chernyak BV; Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russia, 119991. bchernyak1@gmail.com.; Institute of Mitoengineering, Lomonosov Moscow State University, Moscow, Russia, 119991. bchernyak1@gmail.com., Averina OA; Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russia, 119991.; Institute of Mitoengineering, Lomonosov Moscow State University, Moscow, Russia, 119991., Andreev-Andrievskiy AA; Institute of Mitoengineering, Lomonosov Moscow State University, Moscow, Russia, 119991.; Faculty of Biology, Lomonosov Moscow State University, Moscow, Russia, 119991., Zinovkin RA; Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russia, 119991.; Institute of Mitoengineering, Lomonosov Moscow State University, Moscow, Russia, 119991., Lyamzaev KG; Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russia, 119991.; Institute of Mitoengineering, Lomonosov Moscow State University, Moscow, Russia, 119991., Marey MV; Research Center for Obstetrics, Gynecology and Perinatology, Moscow, Russia, 117198., Egorov MV; Institute of Mitoengineering, Lomonosov Moscow State University, Moscow, Russia, 119991., Frolova OJ; Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russia, 119991.; Institute of Mitoengineering, Lomonosov Moscow State University, Moscow, Russia, 119991., Zorov DB; Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russia, 119991., Skulachev MV; Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russia, 119991., Sadovnichii VA; Faculty of Mechanics and Mathematics, Lomonosov Moscow State University, Moscow, Russia, 119991.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2023 Mar 15; Vol. 13 (1), pp. 4326. Date of Electronic Publication: 2023 Mar 15.
DOI: 10.1038/s41598-023-31281-9
Abstrakt: The response to stress involves the activation of pathways leading either to protection from the stress origin, eventually resulting in development of stress resistance, or activation of the rapid death of the organism. Here we hypothesize that mitochondrial reactive oxygen species (mtROS) play a key role in stress-induced programmed death of the organism, which we called "phenoptosis" in 1997. We demonstrate that the synthetic mitochondria-targeted antioxidant SkQ1 (which specifically abolishes mtROS) prevents rapid death of mice caused by four mechanistically very different shocks: (a) bacterial lipopolysaccharide (LPS) shock, (b) shock in response to intravenous mitochondrial injection, (c) cold shock, and (d) toxic shock caused by the penetrating cation C 12 TPP. Importantly, under all these stresses mortality was associated with a strong elevation of the levels of pro-inflammatory cytokines and administration of SkQ1 was able to switch off the cytokine storms. Since the main effect of SkQ1 is the neutralization of mtROS, this study provides evidence for the role of mtROS in the activation of innate immune responses mediating stress-induced death of the organism. We propose that SkQ1 may be used clinically to support patients in critical conditions, such as septic shock, extensive trauma, cooling, and severe infection by bacteria or viruses.
(© 2023. The Author(s).)
Databáze: MEDLINE
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