Rapid and selective generation of H2S within mitochondria protects against cardiac ischemia-reperfusion injury

Autor: Jan Lj. Miljkovic, Nils Burger, Justyna M. Gawel, John F. Mulvey, Abigail A.I. Norman, Takanori Nishimura, Yoshiyuki Tsujihata, Angela Logan, Olga Sauchanka, Stuart T. Caldwell, Jordan L. Morris, Tracy A. Prime, Stefan Warrington, Julien Prudent, Georgina R. Bates, Dunja Aksentijević, Hiran A. Prag, Andrew M. James, Thomas Krieg, Richard C. Hartley, Michael P. Murphy
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Redox Biology, Vol 55, Iss , Pp 102429- (2022)
Druh dokumentu: article
ISSN: 2213-2317
DOI: 10.1016/j.redox.2022.102429
Popis: Mitochondria-targeted H2S donors are thought to protect against acute ischemia-reperfusion (IR) injury by releasing H2S that decreases oxidative damage. However, the rate of H2S release by current donors is too slow to be effective upon administration following reperfusion. To overcome this limitation here we develop a mitochondria-targeted agent, MitoPerSulf that very rapidly releases H2S within mitochondria. MitoPerSulf is quickly taken up by mitochondria, where it reacts with endogenous thiols to generate a persulfide intermediate that releases H2S. MitoPerSulf is acutely protective against cardiac IR injury in mice, due to the acute generation of H2S that inhibits respiration at cytochrome c oxidase thereby preventing mitochondrial superoxide production by lowering the membrane potential. Mitochondria-targeted agents that rapidly generate H2S are a new class of therapy for the acute treatment of IR injury.
Databáze: Directory of Open Access Journals