title: 3, 4-dihydroxyl-phenyl lactic acid restores NADH dehydrogenase 1 α subunit 10 to ameliorate cardiac reperfusion injury.
abstract: The present study aimed to detect the role of 3, 4-dihydroxyl-phenyl lactic acid (DLA) during ischemia/reperfusion (I/R) induced myocardial injury with emphasis on the underlying mechanism of DLA antioxidant. Male Spragu-Dawley (SD) rats were subjected to left descending artery occlusion followed by reperfusion. Treatment with DLA ameliorated myocardial structure and function disorder, blunted the impairment of Complex I activity and mitochondrial function after I/R. The results of 2-D fluorescence difference gel electrophoresis revealed that DLA prevented the decrease in NDUFA10 expression, one of the subunits of Complex I. To find the target of DLA, the binding affinity of Sirtuin 1 (SIRT1) to DLA and DLA derivatives with replaced two phenolic hydroxyls was detected using surface plasmon resonance and bilayer interferometry. The results showed that DLA could activate SIRT1 after I/R probably by binding to this protein, depending on phenolic hydroxyl. Moreover, the importance of SIRT1 to DLA effectiveness was confirmed through siRNA transfection in vitro. These results demonstrated that DLA was able to prevent I/R induced decrease in NDUFA10 expression, improve Complex I activity and mitochondrial function, eventually attenuate cardiac structure and function injury after I/R, which was possibly related to its ability of binding to and activating SIRT1.
authors.affiliation: 1] Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China [2] Department of Integration of Traditional Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing, China.
authors.forename: Xiao-Yuan
authors.initials: XY
authors.lastname: Yang
authors.affiliation: Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China.
authors.forename: Ke
authors.initials: K
authors.lastname: He
authors.affiliation: Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China.
authors.forename: Chun-Shui
authors.initials: CS
authors.lastname: Pan
authors.affiliation: Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Li
authors.affiliation: Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China.
authors.forename: Yu-Ying
authors.initials: YY
authors.lastname: Liu
authors.affiliation: Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Yan
authors.affiliation: Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China.
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Wei
authors.affiliation: Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China.
authors.forename: Bai-He
authors.initials: BH
authors.lastname: Hu
authors.affiliation: Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Chang
authors.affiliation: 1] Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China [2] Department of Integration of Traditional Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing, China.
authors.forename: Xiao-Wei
authors.initials: XW
authors.lastname: Mao
authors.affiliation: 1] Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China [2] Department of Integration of Traditional Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing, China.
authors.forename: Dan-Dan
authors.initials: DD
authors.lastname: Huang
authors.affiliation: Department of Biophysics, Peking University Health Science Center, Beijing, China.
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Wang
authors.affiliation: Department of Pathophysiology and Key Laboratory of Proteomics of Guangdong Province, Southern Medical University, Guangzhou, China.
authors.forename: Shui-Wang
authors.initials: SW
authors.lastname: Hu
authors.affiliation: Department of Pathophysiology and Key Laboratory of Proteomics of Guangdong Province, Southern Medical University, Guangzhou, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China.
authors.forename: Guo-Cheng
authors.initials: GC
authors.lastname: Wang
authors.affiliation: Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China.
authors.forename: Jing-Yu
authors.initials: JY
authors.lastname: Fan
authors.affiliation: Angiogenesis &Chinese Medicine Laboratory, Department of Pharmacology, University of Cambridge, UK.
authors.forename: Tai-Ping
authors.initials: TP
authors.lastname: Fan
authors.affiliation: 1] Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China [2] Department of Integration of Traditional Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing, China [3] Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine of the People's Republic of China [4] Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of the People's Republic of China.
authors.forename: Jing-Yan
authors.initials: JY
authors.lastname: Han
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000494:pharmacology; D002460:Cell Line; D004195:Disease Models, Animal; D042967:Electron Transport Complex I / Q000378:metabolism; D015870:Gene Expression; D019344:Lactic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology*; D007962:Leukocytes / Q000473:pathology; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D009245:NADH Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D056564:Sirtuin 1 / Q000378:metabolism; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D002316:Cardiotonic Agents; D021122:Protein Subunits; D017382:Reactive Oxygen Species; D019344:Lactic Acid; D009245:NADH Dehydrogenase; D056564:Sirtuin 1; D042967:Electron Transport Complex I