Frontiers in Physiology (Jun 2021)
Quantitative Proteomics Reveal That Metabolic Improvement Contributes to the Cardioprotective Effect of T89 on Isoproterenol-Induced Cardiac Injury
- Xiao-Hong Wei,
- Xiao-Hong Wei,
- Xiao-Hong Wei,
- Xiao-Hong Wei,
- Xiao-Hong Wei,
- Xiao-Hong Wei,
- Xiao Guo,
- Xiao Guo,
- Xiao Guo,
- Xiao Guo,
- Xiao Guo,
- Xiao Guo,
- Chun-Shui Pan,
- Chun-Shui Pan,
- Chun-Shui Pan,
- Chun-Shui Pan,
- Chun-Shui Pan,
- Huan Li,
- Huan Li,
- Huan Li,
- Huan Li,
- Huan Li,
- Huan Li,
- Yuan-Chen Cui,
- Yuan-Chen Cui,
- Yuan-Chen Cui,
- Yuan-Chen Cui,
- Yuan-Chen Cui,
- Li Yan,
- Li Yan,
- Li Yan,
- Li Yan,
- Li Yan,
- Jing-Yu Fan,
- Jing-Yu Fan,
- Jing-Yu Fan,
- Jing-Na Deng,
- Jing-Na Deng,
- Jing-Na Deng,
- Jing-Na Deng,
- Jing-Na Deng,
- Bai-He Hu,
- Bai-He Hu,
- Bai-He Hu,
- Bai-He Hu,
- Bai-He Hu,
- Xin Chang,
- Xin Chang,
- Xin Chang,
- Xin Chang,
- Xin Chang,
- Shu-Ya He,
- Shu-Ya He,
- Shu-Ya He,
- Shu-Ya He,
- Shu-Ya He,
- Shu-Ya He,
- Lu-Lu Yan,
- Lu-Lu Yan,
- Lu-Lu Yan,
- Lu-Lu Yan,
- Lu-Lu Yan,
- Kai Sun,
- Kai Sun,
- Kai Sun,
- Kai Sun,
- Kai Sun,
- Chuan-She Wang,
- Chuan-She Wang,
- Chuan-She Wang,
- Chuan-She Wang,
- Chuan-She Wang,
- Chuan-She Wang,
- Jing-Yan Han,
- Jing-Yan Han,
- Jing-Yan Han,
- Jing-Yan Han,
- Jing-Yan Han,
- Jing-Yan Han
Affiliations
- Xiao-Hong Wei
- Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing, China
- Xiao-Hong Wei
- Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China
- Xiao-Hong Wei
- Academy of Integration of Chinese and Western Medicine, Peking University Health Science Center, Beijing, China
- Xiao-Hong Wei
- Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine, Beijing, China
- Xiao-Hong Wei
- Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine, Beijing, China
- Xiao-Hong Wei
- State Key Laboratory of Core Technology in Innovative Chinese Medicine, Tianjin, China
- Xiao Guo
- Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing, China
- Xiao Guo
- Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China
- Xiao Guo
- Academy of Integration of Chinese and Western Medicine, Peking University Health Science Center, Beijing, China
- Xiao Guo
- Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine, Beijing, China
- Xiao Guo
- Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine, Beijing, China
- Xiao Guo
- State Key Laboratory of Core Technology in Innovative Chinese Medicine, Tianjin, China
- Chun-Shui Pan
- Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China
- Chun-Shui Pan
- Academy of Integration of Chinese and Western Medicine, Peking University Health Science Center, Beijing, China
- Chun-Shui Pan
- Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine, Beijing, China
- Chun-Shui Pan
- Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine, Beijing, China
- Chun-Shui Pan
- State Key Laboratory of Core Technology in Innovative Chinese Medicine, Tianjin, China
- Huan Li
- Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing, China
- Huan Li
- Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China
- Huan Li
- Academy of Integration of Chinese and Western Medicine, Peking University Health Science Center, Beijing, China
- Huan Li
- Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine, Beijing, China
- Huan Li
- Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine, Beijing, China
- Huan Li
- State Key Laboratory of Core Technology in Innovative Chinese Medicine, Tianjin, China
- Yuan-Chen Cui
- Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China
- Yuan-Chen Cui
- Academy of Integration of Chinese and Western Medicine, Peking University Health Science Center, Beijing, China
- Yuan-Chen Cui
- Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine, Beijing, China
- Yuan-Chen Cui
- Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine, Beijing, China
- Yuan-Chen Cui
- State Key Laboratory of Core Technology in Innovative Chinese Medicine, Tianjin, China
- Li Yan
- Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China
- Li Yan
- Academy of Integration of Chinese and Western Medicine, Peking University Health Science Center, Beijing, China
- Li Yan
- Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine, Beijing, China
- Li Yan
- Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine, Beijing, China
- Li Yan
- State Key Laboratory of Core Technology in Innovative Chinese Medicine, Tianjin, China
- Jing-Yu Fan
- Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China
- Jing-Yu Fan
- Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine, Beijing, China
- Jing-Yu Fan
- State Key Laboratory of Core Technology in Innovative Chinese Medicine, Tianjin, China
- Jing-Na Deng
- Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China
- Jing-Na Deng
- Academy of Integration of Chinese and Western Medicine, Peking University Health Science Center, Beijing, China
- Jing-Na Deng
- Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine, Beijing, China
- Jing-Na Deng
- Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine, Beijing, China
- Jing-Na Deng
- State Key Laboratory of Core Technology in Innovative Chinese Medicine, Tianjin, China
- Bai-He Hu
- Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China
- Bai-He Hu
- Academy of Integration of Chinese and Western Medicine, Peking University Health Science Center, Beijing, China
- Bai-He Hu
- Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine, Beijing, China
- Bai-He Hu
- Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine, Beijing, China
- Bai-He Hu
- State Key Laboratory of Core Technology in Innovative Chinese Medicine, Tianjin, China
- Xin Chang
- Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China
- Xin Chang
- Academy of Integration of Chinese and Western Medicine, Peking University Health Science Center, Beijing, China
- Xin Chang
- Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine, Beijing, China
- Xin Chang
- Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine, Beijing, China
- Xin Chang
- State Key Laboratory of Core Technology in Innovative Chinese Medicine, Tianjin, China
- Shu-Ya He
- Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing, China
- Shu-Ya He
- Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China
- Shu-Ya He
- Academy of Integration of Chinese and Western Medicine, Peking University Health Science Center, Beijing, China
- Shu-Ya He
- Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine, Beijing, China
- Shu-Ya He
- Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine, Beijing, China
- Shu-Ya He
- State Key Laboratory of Core Technology in Innovative Chinese Medicine, Tianjin, China
- Lu-Lu Yan
- Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China
- Lu-Lu Yan
- Academy of Integration of Chinese and Western Medicine, Peking University Health Science Center, Beijing, China
- Lu-Lu Yan
- Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine, Beijing, China
- Lu-Lu Yan
- Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine, Beijing, China
- Lu-Lu Yan
- State Key Laboratory of Core Technology in Innovative Chinese Medicine, Tianjin, China
- Kai Sun
- Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China
- Kai Sun
- Academy of Integration of Chinese and Western Medicine, Peking University Health Science Center, Beijing, China
- Kai Sun
- Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine, Beijing, China
- Kai Sun
- Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine, Beijing, China
- Kai Sun
- State Key Laboratory of Core Technology in Innovative Chinese Medicine, Tianjin, China
- Chuan-She Wang
- Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing, China
- Chuan-She Wang
- Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China
- Chuan-She Wang
- Academy of Integration of Chinese and Western Medicine, Peking University Health Science Center, Beijing, China
- Chuan-She Wang
- Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine, Beijing, China
- Chuan-She Wang
- Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine, Beijing, China
- Chuan-She Wang
- State Key Laboratory of Core Technology in Innovative Chinese Medicine, Tianjin, China
- Jing-Yan Han
- Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing, China
- Jing-Yan Han
- Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China
- Jing-Yan Han
- Academy of Integration of Chinese and Western Medicine, Peking University Health Science Center, Beijing, China
- Jing-Yan Han
- Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine, Beijing, China
- Jing-Yan Han
- Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine, Beijing, China
- Jing-Yan Han
- State Key Laboratory of Core Technology in Innovative Chinese Medicine, Tianjin, China
- DOI
- https://doi.org/10.3389/fphys.2021.653349
- Journal volume & issue
-
Vol. 12
Abstract
BackgroundT89, a traditional Chinese medicine, has passed phase II, and is undergoing phase III clinical trials for treatment of ischemic cardiovascular disease by the US FDA. However, the role of T89 on isoproterenol (ISO)-induced cardiac injury is unknown. The present study aimed to explore the effect and underlying mechanism of T89 on ISO-induced cardiac injury.MethodsMale Sprague-Dawley rats received subcutaneous injection of ISO saline solution at 24 h intervals for the first 3 days and then at 48 h intervals for the next 12 days. T89 at dose of 111.6 and 167.4 mg/kg was administrated by gavage for 15 consecutive days. Rat survival rate, cardiac function evaluation, morphological observation, quantitative proteomics, and Western blotting analysis were performed.ResultsT89 obviously improved ISO-induced low survival rate, attenuated ISO-evoked cardiac injury, as evidenced by myocardial blood flow, heart function, and morphology. Quantitative proteomics revealed that the cardioprotective effect of T89 relied on the regulation of metabolic pathways, including glycolipid metabolism and energy metabolism. T89 inhibited the enhancement of glycolysis, promoted fatty acid oxidation, and restored mitochondrial oxidative phosphorylation by regulating Eno1, Mcee, Bdh1, Ces1c, Apoc2, Decr1, Acaa2, Cbr4, ND2, Cox 6a, Cox17, ATP5g, and ATP5j, thus alleviated oxidative stress and energy metabolism disorder and ameliorated cardiac injury after ISO. The present study also verified that T89 significantly restrained ISO-induced increase of HSP70/HSP40 and suppressed the phosphorylation of ERK, further restored the expression of CX43, confirming the protective role of T89 in cardiac hypertrophy. Proteomics data are available via ProteomeXchange with identifier PXD024641.ConclusionT89 reduced mortality and improves outcome in the model of ISO-induced cardiac injury and the cardioprotective role of T89 is correlated with the regulation of glycolipid metabolism, recovery of mitochondrial function, and improvement of myocardial energy.
Keywords
- glycolysis
- fatty acid oxidation
- energy metabolism
- mitochondrial electron transport chain
- cardiac hypertrophy
