Dietary methionine restriction attenuates renal ischaemia/reperfusion-induced myocardial injury by activating the CSE/H2S/ERS pathway in diabetic mice

J Cell Mol Med. 2020 Sep;24(17):9890-9897. doi: 10.1111/jcmm.15578. Epub 2020 Aug 13.

Abstract

Methionine restrictive diet may alleviate ischaemia/reperfusion (I/R)-induced myocardial injury, but its underlying mechanism remains unclear. HE staining was performed to evaluate the myocardial injury caused by I/R and the effect of methionine-restricted diet (MRD) in I/R mice. IHC and Western blot were carried out to analyse the expression of CSE, CHOP and active caspase3 in I/R mice and hypoxia/reoxygenation (H/R) cells. TUNEL assay and flow cytometry were used to assess the apoptotic status of I/R mice and H/R cells. MTT was performed to analyse the proliferation of H/R cells. H2S assay was used to evaluate the concentration of H2S in the myocardial tissues and peripheral blood of I/R mice. I/R-induced mediated myocardial injury and apoptosis were partially reversed by methionine-restricted diet (MRD) via the down-regulation of CSE expression and up-regulation of CHOP and active caspase3 expression. The decreased H2S concentration in myocardial tissues and peripheral blood of I/R mice was increased by MRD. Accordingly, in a cellular model of I/R injury established with H9C2 cells, cell proliferation was inhibited, cell apoptosis was increased, and the expressions of CSE, CHOP and active caspase3 were dysregulated, whereas NaHS treatment alleviated the effect of I/R injury in H9C2 cells in a dose-dependent manner. This study provided a deep insight into the mechanism underlying the role of MRD in I/R-induced myocardial injury.

Keywords: CSE; ERS; apoptosis; dietary methionine restriction; hydrogen disulphide; ischaemia; reperfusion.

MeSH terms

  • Acute Kidney Injury / complications
  • Acute Kidney Injury / diet therapy
  • Acute Kidney Injury / metabolism*
  • Animals
  • Apoptosis / genetics
  • Caspase 3 / genetics
  • Cell Proliferation / drug effects
  • Diabetes Mellitus, Experimental / diet therapy*
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Experimental / pathology
  • Humans
  • Kidney
  • Methionine / genetics
  • Methionine / metabolism*
  • Mice
  • Mice, Inbred NOD / genetics
  • Mice, Inbred NOD / metabolism
  • MicroRNAs / genetics
  • Myocardial Reperfusion Injury / diet therapy
  • Myocardial Reperfusion Injury / etiology
  • Myocardial Reperfusion Injury / metabolism*
  • Myocardium / metabolism
  • Reperfusion Injury / complications
  • Reperfusion Injury / diet therapy
  • Reperfusion Injury / metabolism
  • Signal Transduction / genetics
  • Sulfites / pharmacology
  • Transcription Factor CHOP / genetics

Substances

  • Ddit3 protein, mouse
  • MicroRNAs
  • Sulfites
  • Transcription Factor CHOP
  • sodium hydrogen sulfite
  • Methionine
  • Caspase 3