Journal
DRUG DESIGN DEVELOPMENT AND THERAPY
Volume 13, Issue -, Pages 2331-2342Publisher
DOVE MEDICAL PRESS LTD
DOI: 10.2147/DDDT.S194753
Keywords
myocardial ischemia reperfusion injury; lycopene; mitochondrial permeability transition pore; apoptosis
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Funding
- National Natural Science Foundation of China [81670320, 81800232]
- Natural Science Foundation of Liaoning Province [201602826]
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Background: Mitochondria permeability transition pore (MPTP) is an important therapeutic target for myocardial ischemia-reperfusion injury (MIRI). Lycopene (LP) is a potent antioxidant extracted from the mature fruits of plants and has been reported to protect against MIRI; however, its mechanism of action has yet to be completely elucidated. The present study aimed to investigate the role of MPTP in the cardioprotection of LP. Methods: H9c2 cells were pretreated with LP for 12 hrs and were subjected to 12-hr hypoxia/1-hr re-oxygenation, and cell viability was measured by a Cell Counting Kit-8 (CCK-8) assay. Male rats were subsequently intraperitoneally injected with LP for 5 consecutive days. At 24 hrs following the final injection, the rat hearts were isolated and subjected to 30-min ischemia/120-min reperfusion using Langendorff apparatus. The myocardial infarct size was measured by a TTC stain. Opening of the MPTP was induced by CaCl2 and measured by colorimetry. The change in mitochondrial transmembrane potential (Delta Psi m) was observed under a fluorescence microscope. Apoptosis was measured by flow cytometry and a TUNEL stain, and the expression of apoptosis-related proteins was detected by Western blotting. Results: LP pretreatment significantly increased cell viability, reduced myocardial infarct size and decreased the apoptosis rate. In addition, opening and the decrease of Delta Psi m were attenuated by LP and the expressions of cytochrome c, APAF-1, cleaved caspase-9 and cleaved caspase-3 were also decreased by LP. However, these beneficial effects on MIRI were abrogated by the MPTP opener (atractyloside). Furthermore, LP treatment markedly increased Bcl-2 expression, decreased Bax expression and the Bax/Bcl-2 ratio. Conclusion: The results of the present study demonstrated that LP protects against MIRI by inhibiting MPTP opening, partly through the modulation of Bax and Bcl-2.
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