BDNF mimetic 7,8-dihydroxyflavone rescues rotenone-induced cytotoxicity in cardiomyocytes by ameliorating mitochondrial dysfunction.

Autor: Hang PZ; Department of Pharmacy, Clinical Medical College, Yangzhou University, Northern Jiangsu People's Hospital, Yangzhou, 225001, China., Ge FQ; Department of Pharmacy, Clinical Medical College, Yangzhou University, Northern Jiangsu People's Hospital, Yangzhou, 225001, China; Medical College, Yangzhou University, Yangzhou, 225009, China., Zhang MR; Department of Pharmacy, Clinical Medical College, Yangzhou University, Northern Jiangsu People's Hospital, Yangzhou, 225001, China; College of Pharmacy, Dalian Medical University, Dalian, 116044, China., Li QH; Department of Pharmacy, Clinical Medical College, Yangzhou University, Northern Jiangsu People's Hospital, Yangzhou, 225001, China; Medical College, Yangzhou University, Yangzhou, 225009, China., Yu HQ; Department of Pharmacy, Clinical Medical College, Yangzhou University, Northern Jiangsu People's Hospital, Yangzhou, 225001, China; College of Pharmacy, Dalian Medical University, Dalian, 116044, China., Song YC; Department of Pharmacy, Clinical Medical College, Yangzhou University, Northern Jiangsu People's Hospital, Yangzhou, 225001, China; Medical College, Yangzhou University, Yangzhou, 225009, China., Guo DD; Department of Pharmacy, Clinical Medical College, Yangzhou University, Northern Jiangsu People's Hospital, Yangzhou, 225001, China; Medical College, Yangzhou University, Yangzhou, 225009, China., Zhao J; Department of Pharmacy, Clinical Medical College, Yangzhou University, Northern Jiangsu People's Hospital, Yangzhou, 225001, China. Electronic address: zhaojinghmu@163.com., Zhu H; Department of Pharmacy, Clinical Medical College, Yangzhou University, Northern Jiangsu People's Hospital, Yangzhou, 225001, China. Electronic address: daitutu990201@163.com.
Jazyk: angličtina
Zdroj: Free radical biology & medicine [Free Radic Biol Med] 2023 Mar; Vol. 198, pp. 83-91. Date of Electronic Publication: 2023 Feb 09.
DOI: 10.1016/j.freeradbiomed.2023.02.006
Abstrakt: The relationship between mitochondrial dysfunction and cardiovascular disease pathogenesis is well recognized. 7,8-Dihydroxyflavone (7,8-DHF), a mimetic of brain-derived neurotrophic factor, inhibits mitochondrial impairments and improves cardiac function. However, the regulatory role of 7,8-DHF in the mitochondrial function of cardiomyocytes is not fully understood. To investigate the potential mito-protective effects of 7,8-DHF in cardiomyocytes, we treated H9c2 or HL-1 cells with the mitochondrial respiratory complex I inhibitor rotenone (Rot) as an in vitro model of mitochondrial dysfunction. We found that 7,8-DHF effectively eliminated various concentrations of Rot-induced cell death and reduced lactate dehydrogenase release. 7,8-DHF significantly improved mitochondrial membrane potential and inhibited mitochondrial reactive oxygen species. Moreover, 7,8-DHF decreased routine and leak respiration, restored protein levels of mitochondrial complex I-IV, and increased ATP production in Rot-treated H9c2 cells. The protective role of 7,8-DHF in Rot-induced damage was validated in HL-1 cells. Nuclear phosphorylation protein expression of signal transducer and activator of transcription 3 (STAT3) was significantly increased by 7,8-DHF. The present study suggests that 7,8-DHF rescues Rot-induced cytotoxicity by inhibiting mitochondrial dysfunction and promoting nuclear translocation of p-STAT3 in cardiomyocytes, thus nominating 7,8-DHF as a new pharmacological candidate agent against mitochondrial dysfunction in cardiac diseases.
Competing Interests: Declaration of competing interest The authors declare no conflicts of interest.
(Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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