title: Lycopene protects against apoptosis in hypoxia/reoxygenation‑induced H9C2 myocardioblast cells through increased autophagy.
abstract: Lycopene (Ly), the most common type of antioxidant in the majority of diet types, provides tolerance to ischemia/reperfusion injury. However, the underlying mechanism of the protective effects observed following Ly administration remains poorly investigated. The aim of the current study was to investigate whether Ly prevents damage to hypoxia/reoxygenation (HR)‑induced H9C2 myocardioblasts in an autophagy‑dependent manner. The levels of autophagic markers were detected using western blotting, the level of apoptosis was detected using western blotting and flow cytometry. The activation of autophagy was impaired via knockdown of the expression of 'microtubule‑associated protein 1‑light chain 3β (MAP1LC3B)' and 'Beclin 1'. After 16 h hypoxia, followed by 2 h reoxygenation, the expression levels of the microtubule‑associated protein 1A/1B‑light chain 3 (LC3) and Βeclin 1 autophagic biomarkers, and cell viability were reduced, whereas the percentage of apoptotic cells, and the expression levels of the Bax/B‑cell lymphoma 2 (Bcl‑2) and active caspase‑3 apoptotic biomarkers were increased. Pre‑incubation of the cells with different Ly concentrations reversed the HR‑induced inhibition of autophagy and cell viability, and the HR‑induced elevation in apoptotic levels. The induction of autophagy was accompanied by reduced apoptosis, and decreased expression levels of Bax/Bcl‑2 and active caspase‑3. In addition, the impairment of autophagy by silencing the expression of MAP1LC3B and Beclin 1 accelerated HR‑induced H9C2 cell apoptosis and the Ly‑mediated protective effects disappeared. Furthermore, Bax/Bcl‑2 and active caspase‑3 expression levels were increased. Moreover, Ly‑induced autophagy was associated with increased adenosine monophosphate kinase (AMPK) phosphorylation. Suppressed AMPK phosphorylation using compound C terminates Ly‑mediated cytoprotective effects. Ly treatment improves cell viability and reduces apoptosis as a result of the activation of the adaptive autophagic response on HR‑induced H9C2 myocardioblasts. AMPK phosphorylation may be involved in the progression.
authors.affiliation: Institution of Cardiology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Fei
authors.initials: F
authors.lastname: Chen
authors.affiliation: Institution of Cardiology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Ze-Wei
authors.initials: ZW
authors.lastname: Sun
authors.affiliation: Institution of Cardiology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Li-Fang
authors.initials: LF
authors.lastname: Ye
authors.affiliation: Department of Cardiology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310012, P.R. China.
authors.forename: Guo-Sheng
authors.initials: GS
authors.lastname: Fu
authors.affiliation: Department of Ultrasound, The Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Mou
authors.affiliation: Institution of Cardiology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Shen-Jiang
authors.initials: SJ
authors.lastname: Hu
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects*; D000071186:Beclin-1; D002338:Carotenoids / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D000077276:Lycopene; D008869:Microtubule-Associated Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D032446:Myoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000975:Antioxidants; D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; C512829:Becn1 protein, rat; D008869:Microtubule-Associated Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D051028:bcl-2-Associated X Protein; D002338:Carotenoids; D055372:AMP-Activated Protein Kinases; D053148:Caspase 3; D000077276:Lycopene