The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Hydrogen sulfide restores cardioprotective effects of remote ischemic preconditioning in aged rats via HIF-1α/Nrf2 signaling pathway

  • Wang, Haixia (Department of Cardiovascular, First Affiliated Hospital of Xi'an Jiaotong University) ;
  • Shi, Xin (Department of Cardiovascular, Affiliated Zhongshan Hospital of Dalian University) ;
  • Cheng, Longlong (Department of Judicial Expertise, Affiliated Zhongshan Hospital of Dalian University) ;
  • Han, Jie (Department of Cardiovascular, Affiliated Zhongshan Hospital of Dalian University) ;
  • Mu, Jianjun (Department of Cardiovascular, First Affiliated Hospital of Xi'an Jiaotong University)
  • Received : 2020.11.23
  • Accepted : 2021.02.05
  • Published : 2021.05.01
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Abstract

The present study explored the therapeutic potential of hydrogen sulfide (H2S) in restoring aging-induced loss of cardioprotective effect of remote ischemic preconditioning (RIPC) along with the involvement of signaling pathways. The left hind limb was subjected to four short cycles of ischemia and reperfusion (IR) in young and aged male rats to induce RIPC. The hearts were subjected to IR injury on the Langendorff apparatus after 24 h of RIPC. The measurement of lactate dehydrogenase, creatine kinase and cardiac troponin served to assess the myocardial injury. The levels of H2S, cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), nuclear factor erythroid 2-related factor 2 (Nrf2), and hypoxia-inducible factor (HIF-1α) were also measured. There was a decrease in cardioprotection in RIPC-subjected old rats in comparison to young rats along with a reduction in the myocardial levels of H2S, CBS, CSE, HIF-1α, and nuclear: cytoplasmic Nrf2 ratio. Supplementation with sodium hydrogen sulfide (NaHS, an H2S donor) and l-cysteine (H2S precursor) restored the cardioprotective actions of RIPC in old hearts. It increased the levels of H2S, HIF-1α, and Nrf2 ratio without affecting CBS and CSE. YC-1 (HIF-1α antagonist) abolished the effects of NaHS and l-cysteine in RIPC-subjected old rats by decreasing the Nrf2 ratio and HIF-1α levels, without altering H2S. The late phase of cardioprotection of RIPC involves an increase in the activity of H2S biosynthetic enzymes, which increases the levels of H2S to upregulate HIF-1α and Nrf2. H2S has the potential to restore aging-induced loss of cardioprotective effects of RIPC by upregulating HIF-1α/Nrf2 signaling.

Keywords

References

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