Canonical transient receptor potential channel 1 aggravates myocardial ischemia-and-reperfusion injury by upregulating reactive oxygen species

Hui-Nan Zhang; Meng Zhang; Wen Tian; Wei Quan; Fan Song; Shao-Yuan Liu; Xiao-Xiao Liu; Dan Mo; Yang Sun; Yuan-Yuan Gao; Wen Ye; Ying-Da Feng; Chang-Yang Xing; Chen Ye; Lei Zhou; Jing-Ru Meng; Wei Cao; Xiao-Qiang Li

Journal of Pharmaceutical Analysis (Nov 2023)

Canonical transient receptor potential channel 1 aggravates myocardial ischemia-and-reperfusion injury by upregulating reactive oxygen species

Hui-Nan Zhang,
Meng Zhang,
Wen Tian,
Wei Quan,
Fan Song,
Shao-Yuan Liu,
Xiao-Xiao Liu,
Dan Mo,
Yang Sun,
Yuan-Yuan Gao,
Wen Ye,
Ying-Da Feng,
Chang-Yang Xing,
Chen Ye,
Lei Zhou,
Jing-Ru Meng,
Wei Cao,
Xiao-Qiang Li

Affiliations

Hui-Nan Zhang: Department of Health Management, Second Affiliated Hospital, Fourth Military Medical University, Xi'an, 710038, China; Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China; Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China
Meng Zhang: Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China; Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China; Shaanxi Key Laboratory of “Qin Medicine” Research and Development, Shaanxi Administration of Traditional Chinese Medicine, Xi'an, 710032, China
Wen Tian: Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China; Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China; Shaanxi Key Laboratory of “Qin Medicine” Research and Development, Shaanxi Administration of Traditional Chinese Medicine, Xi'an, 710032, China
Wei Quan: Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China; Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China; Shaanxi Key Laboratory of “Qin Medicine” Research and Development, Shaanxi Administration of Traditional Chinese Medicine, Xi'an, 710032, China
Fan Song: Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China; Institute of Materia Medica, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China
Shao-Yuan Liu: Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China; Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China; Shaanxi Key Laboratory of “Qin Medicine” Research and Development, Shaanxi Administration of Traditional Chinese Medicine, Xi'an, 710032, China
Xiao-Xiao Liu: Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China; Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China
Dan Mo: Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China; Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China
Yang Sun: Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China; Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China
Yuan-Yuan Gao: Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China; Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China
Wen Ye: Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China; Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China; Shaanxi Key Laboratory of “Qin Medicine” Research and Development, Shaanxi Administration of Traditional Chinese Medicine, Xi'an, 710032, China
Ying-Da Feng: Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China; Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China; Shaanxi Key Laboratory of “Qin Medicine” Research and Development, Shaanxi Administration of Traditional Chinese Medicine, Xi'an, 710032, China
Chang-Yang Xing: Department of Ultrasound Diagnostics, Second Affiliated Hospital, Fourth Military Medical University, Xi'an, 710038, China
Chen Ye: Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China; Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China
Lei Zhou: Department of Pharmacy, School of Chemistry & Pharmacy, Northwest A&F University, Yangling, Shaanxi, 712100, China
Jing-Ru Meng: Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China; Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China; Shaanxi Key Laboratory of “Qin Medicine” Research and Development, Shaanxi Administration of Traditional Chinese Medicine, Xi'an, 710032, China
Wei Cao: Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China; Department of Pharmacy, School of Chemistry & Pharmacy, Northwest A&F University, Yangling, Shaanxi, 712100, China; Corresponding author. Department of Pharmacy, School of Chemistry & Pharmacy, Northwest A&F University, Yangling, Shaanxi, 712100, China.
Xiao-Qiang Li: Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China; Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China; Shaanxi Key Laboratory of “Qin Medicine” Research and Development, Shaanxi Administration of Traditional Chinese Medicine, Xi'an, 710032, China; Corresponding author. Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China.

Journal volume & issue: Vol. 13, no. 11
pp. 1309 – 1325

Abstract

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The canonical transient receptor potential channel (TRPC) proteins form Ca2+-permeable cation channels that are involved in various heart diseases. However, the roles of specific TRPC proteins in myocardial ischemia/reperfusion (I/R) injury remain poorly understood. We observed that TRPC1 and TRPC6 were highly expressed in the area at risk (AAR) in a coronary artery ligation induced I/R model. Trpc1−/− mice exhibited improved cardiac function, lower serum Troponin T and serum creatine kinase level, smaller infarct volume, less fibrotic scars, and fewer apoptotic cells after myocardial-I/R than wild-type or Trpc6−/− mice. Cardiomyocyte-specific knockdown of Trpc1 using adeno-associated virus 9 mitigated myocardial I/R injury. Furthermore, Trpc1 deficiency protected adult mouse ventricular myocytes (AMVMs) and HL-1 cells from death during hypoxia/reoxygenation (H/R) injury. RNA-sequencing-based transcriptome analysis revealed differential expression of genes related to reactive oxygen species (ROS) generation in Trpc1−/− cardiomyocytes. Among these genes, oxoglutarate dehydrogenase-like (Ogdhl) was markedly downregulated. Moreover, Trpc1 deficiency impaired the calcineurin (CaN)/nuclear factor-kappa B (NF-κB) signaling pathway in AMVMs. Suppression of this pathway inhibited Ogdhl upregulation and ROS generation in HL-1 cells under H/R conditions. Chromatin immunoprecipitation assays confirmed NF-κB binding to the Ogdhl promoter. The cardioprotective effect of Trpc1 deficiency was canceled out by overexpression of NF-κB and Ogdhl in cardiomyocytes. In conclusion, our findings reveal that TRPC1 is upregulated in the AAR following myocardial I/R, leading to increased Ca2+ influx into associated cardiomyocytes. Subsequently, this upregulates Ogdhl expression through the CaN/NF-κB signaling pathway, ultimately exacerbating ROS production and aggravating myocardial I/R injury.

Published in Journal of Pharmaceutical Analysis

ISSN: 2095-1779 (Print); 2214-0883 (Online)
Publisher: Elsevier
Country of publisher: China
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: http://www.journals.elsevier.com/journal-of-pharmaceutical-analysis/

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