Cardioprotection effects of LPTC-5 involve mitochondrial protection and dynamics

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We recently designed and synthesized a series of novel levodopa–peptide–TEMPO conjugates (LPTCs). Among these compounds, LPTC-5 possesses both free-radical scavenging potential and mitochondrial fusion-promoting activity. The free-radical scavenging capacity of LPTC-5 was confirmed using a PC12 cell survival assay. LPTC-5 could restore the mitochondrial tubular network following genetically induced fragmentation. The therapeutic efficacy of LPTC-5 was then examined employing in vitro and in vivo ischemia/reperfusion (I/R) models. LPTC-5 protected cells from mitochondrial reactive oxygen species overproduction and inhibited cytochrome c release in a simulated I/R cellular model. Additionally, LPTC-5 attenuated organ damage in a cardiac I/R animal model. The data suggest that LPTC-5 exerts cardioprotection via modulation of mitochondrial fission/fusion dynamics, ultimately improving mitochondrial function and cardiac function.

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© 2019 American Chemical Society. Publisher’s version of record: https://doi.org/10.1021/acsomega.8b02441

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ACS Omega