L-carnitine ameliorates myocardial injury by alleviating endoplasmic reticulum stress via inhibition of PERK pathway in exertional heatstroke rats
Exertional heatstroke (EHS) is a life-threatening condition with potential for tissues and organs injury, including heart. Effective drug strategies to treat patients with EHS are warranted to unlock the therapeutic potential. Considering the cardioprotective effects of L-carnitine (LC), this study...
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Elsevier
2024-11-01
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844024165334 |
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| author | Bo-Yi Zhang Gen-Lin He Ze-Ze Wang Huan Zhou Xue-Yan Huang Ting-Ting Shen Xiao-Qian Liu Yi-Shan Liu Zhen Luo Ping Li Yu-Long Tan Xue Luo Xue-Sen Yang |
| author_facet | Bo-Yi Zhang Gen-Lin He Ze-Ze Wang Huan Zhou Xue-Yan Huang Ting-Ting Shen Xiao-Qian Liu Yi-Shan Liu Zhen Luo Ping Li Yu-Long Tan Xue Luo Xue-Sen Yang |
| author_sort | Bo-Yi Zhang |
| collection | DOAJ |
| description | Exertional heatstroke (EHS) is a life-threatening condition with potential for tissues and organs injury, including heart. Effective drug strategies to treat patients with EHS are warranted to unlock the therapeutic potential. Considering the cardioprotective effects of L-carnitine (LC), this study aimed to investigate the effects of LC on EHS-induced myocardial injury in rats and to explore the underlying mechanisms. Here, we found that LC exerted a greater protective effect on EHS-induced cardiac dysfunction and mortality, which also significantly attenuated certain negative effects, including increased myocardial apoptosis, pathological changes, and ultrastructural impairment, enhanced activity levels of such serum enzymes as AST, LDH, CK, and CK-MB, reduced BCL-2 expression, increased the expression of cleaved caspase-3 and the critical endoplasmic reticulum stress (ERS) indices like CHOP and GRP78 in EHS rats. Besides, pretreatment of EHS rats with PBA (4-Phenyl butyric acid), a chemical chaperone that attenuates ERS, restored BCL-2 expression, reduced the protein levels of cleaved caspase-3, CHOP, and GRP78. Furthermore, thapsigargin (TG), which induces ERS, enhanced the expression of BAX, cleaved caspase-3, CHOP, and GRP78, attenuated BCL-2 expression, and enhanced mitochondrial impairment in EHS + LC rats. Mechanismly, the protective effects of LC were mediated, at least partly, by inhibiting the activation of PERK pathway against ERS-associated myocardial damage. These results indicate that supplementation of LC might be a potential strategy to reduce myocardial injury by affecting ERS via inhibiting the PERK pathway against EHS. |
| format | Article |
| id | doaj-art-9ae49c2294bf4cf289f70e5aa60c562d |
| institution | DOAJ |
| issn | 2405-8440 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj-art-9ae49c2294bf4cf289f70e5aa60c562d2025-08-20T02:48:58ZengElsevierHeliyon2405-84402024-11-011022e4050210.1016/j.heliyon.2024.e40502L-carnitine ameliorates myocardial injury by alleviating endoplasmic reticulum stress via inhibition of PERK pathway in exertional heatstroke ratsBo-Yi Zhang0Gen-Lin He1Ze-Ze Wang2Huan Zhou3Xue-Yan Huang4Ting-Ting Shen5Xiao-Qian Liu6Yi-Shan Liu7Zhen Luo8Ping Li9Yu-Long Tan10Xue Luo11Xue-Sen Yang12Department of Tropical Medicine, Army Medical University, Chongqing, China; Key Laboratory of Extreme Environmental Medicine, Ministry of Education of China, Army Medical University, Chongqing, ChinaDepartment of Tropical Medicine, Army Medical University, Chongqing, China; Key Laboratory of Extreme Environmental Medicine, Ministry of Education of China, Army Medical University, Chongqing, China; Corresponding author. Department of Tropical Medicine, Army Medical University, 30 Gaotanyan Central Street, Shapingba District, Chongqing, 400038, China.Department of Tropical Medicine, Army Medical University, Chongqing, China; Key Laboratory of Extreme Environmental Medicine, Ministry of Education of China, Army Medical University, Chongqing, ChinaDepartment of Tropical Medicine, Army Medical University, Chongqing, China; Key Laboratory of Extreme Environmental Medicine, Ministry of Education of China, Army Medical University, Chongqing, ChinaDepartment of Tropical Medicine, Army Medical University, Chongqing, China; Key Laboratory of Extreme Environmental Medicine, Ministry of Education of China, Army Medical University, Chongqing, ChinaDepartment of Tropical Medicine, Army Medical University, Chongqing, China; Key Laboratory of Extreme Environmental Medicine, Ministry of Education of China, Army Medical University, Chongqing, ChinaDepartment of Tropical Medicine, Army Medical University, Chongqing, China; Key Laboratory of Extreme Environmental Medicine, Ministry of Education of China, Army Medical University, Chongqing, ChinaDepartment of Tropical Medicine, Army Medical University, Chongqing, China; Key Laboratory of Extreme Environmental Medicine, Ministry of Education of China, Army Medical University, Chongqing, ChinaDepartment of Tropical Medicine, Army Medical University, Chongqing, China; Key Laboratory of Extreme Environmental Medicine, Ministry of Education of China, Army Medical University, Chongqing, ChinaDepartment of Tropical Medicine, Army Medical University, Chongqing, China; Key Laboratory of Extreme Environmental Medicine, Ministry of Education of China, Army Medical University, Chongqing, ChinaDepartment of Tropical Medicine, Army Medical University, Chongqing, China; Key Laboratory of Extreme Environmental Medicine, Ministry of Education of China, Army Medical University, Chongqing, ChinaDepartment of Tropical Medicine, Army Medical University, Chongqing, China; Key Laboratory of Extreme Environmental Medicine, Ministry of Education of China, Army Medical University, Chongqing, ChinaDepartment of Tropical Medicine, Army Medical University, Chongqing, China; Key Laboratory of Extreme Environmental Medicine, Ministry of Education of China, Army Medical University, Chongqing, China; Corresponding author. Department of Tropical Medicine, Army Medical University, 30 Gaotanyan Central Street, Shapingba District, Chongqing, 400038, China.Exertional heatstroke (EHS) is a life-threatening condition with potential for tissues and organs injury, including heart. Effective drug strategies to treat patients with EHS are warranted to unlock the therapeutic potential. Considering the cardioprotective effects of L-carnitine (LC), this study aimed to investigate the effects of LC on EHS-induced myocardial injury in rats and to explore the underlying mechanisms. Here, we found that LC exerted a greater protective effect on EHS-induced cardiac dysfunction and mortality, which also significantly attenuated certain negative effects, including increased myocardial apoptosis, pathological changes, and ultrastructural impairment, enhanced activity levels of such serum enzymes as AST, LDH, CK, and CK-MB, reduced BCL-2 expression, increased the expression of cleaved caspase-3 and the critical endoplasmic reticulum stress (ERS) indices like CHOP and GRP78 in EHS rats. Besides, pretreatment of EHS rats with PBA (4-Phenyl butyric acid), a chemical chaperone that attenuates ERS, restored BCL-2 expression, reduced the protein levels of cleaved caspase-3, CHOP, and GRP78. Furthermore, thapsigargin (TG), which induces ERS, enhanced the expression of BAX, cleaved caspase-3, CHOP, and GRP78, attenuated BCL-2 expression, and enhanced mitochondrial impairment in EHS + LC rats. Mechanismly, the protective effects of LC were mediated, at least partly, by inhibiting the activation of PERK pathway against ERS-associated myocardial damage. These results indicate that supplementation of LC might be a potential strategy to reduce myocardial injury by affecting ERS via inhibiting the PERK pathway against EHS.http://www.sciencedirect.com/science/article/pii/S2405844024165334L-carnitineExertional heatstrokeMyocardial apoptosisEndoplasmic reticulum stressMitochondrial damage |
| spellingShingle | Bo-Yi Zhang Gen-Lin He Ze-Ze Wang Huan Zhou Xue-Yan Huang Ting-Ting Shen Xiao-Qian Liu Yi-Shan Liu Zhen Luo Ping Li Yu-Long Tan Xue Luo Xue-Sen Yang L-carnitine ameliorates myocardial injury by alleviating endoplasmic reticulum stress via inhibition of PERK pathway in exertional heatstroke rats Heliyon L-carnitine Exertional heatstroke Myocardial apoptosis Endoplasmic reticulum stress Mitochondrial damage |
| title | L-carnitine ameliorates myocardial injury by alleviating endoplasmic reticulum stress via inhibition of PERK pathway in exertional heatstroke rats |
| title_full | L-carnitine ameliorates myocardial injury by alleviating endoplasmic reticulum stress via inhibition of PERK pathway in exertional heatstroke rats |
| title_fullStr | L-carnitine ameliorates myocardial injury by alleviating endoplasmic reticulum stress via inhibition of PERK pathway in exertional heatstroke rats |
| title_full_unstemmed | L-carnitine ameliorates myocardial injury by alleviating endoplasmic reticulum stress via inhibition of PERK pathway in exertional heatstroke rats |
| title_short | L-carnitine ameliorates myocardial injury by alleviating endoplasmic reticulum stress via inhibition of PERK pathway in exertional heatstroke rats |
| title_sort | l carnitine ameliorates myocardial injury by alleviating endoplasmic reticulum stress via inhibition of perk pathway in exertional heatstroke rats |
| topic | L-carnitine Exertional heatstroke Myocardial apoptosis Endoplasmic reticulum stress Mitochondrial damage |
| url | http://www.sciencedirect.com/science/article/pii/S2405844024165334 |
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