3, 4-dihydroxyl-phenyl lactic acid restores NADH dehydrogenase 1 α subunit 10 to ameliorate cardiac reperfusion injury

Sci Rep. 2015 Jun 1:5:10739. doi: 10.1038/srep10739.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Cardiotonic Agents / administration & dosage
  • Cardiotonic Agents / pharmacology
  • Cell Line
  • Disease Models, Animal
  • Electron Transport Complex I / metabolism
  • Gene Expression
  • Lactic Acid / administration & dosage
  • Lactic Acid / analogs & derivatives
  • Lactic Acid / pharmacology*
  • Leukocytes / pathology
  • Male
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Myocardial Infarction / metabolism
  • Myocardial Infarction / pathology
  • Myocardial Reperfusion Injury / drug therapy
  • Myocardial Reperfusion Injury / metabolism*
  • Myocardial Reperfusion Injury / pathology*
  • Myocardial Reperfusion Injury / physiopathology
  • NADH Dehydrogenase / genetics
  • NADH Dehydrogenase / metabolism*
  • Protein Binding
  • Protein Subunits / genetics
  • Protein Subunits / metabolism*
  • Rats
  • Reactive Oxygen Species / metabolism
  • Sirtuin 1 / metabolism
  • Ventricular Function, Left / drug effects

Substances

  • Cardiotonic Agents
  • Protein Subunits
  • Reactive Oxygen Species
  • Lactic Acid
  • NADH Dehydrogenase
  • Sirtuin 1
  • Electron Transport Complex I