Cardioprotection by nicotinamide mononucleotide (NMN): Involvement of glycolysis and acidic pH

Cardioprotection by nicotinamide mononucleotide (NMN): Involvement of glycolysis and acidic pH

NMN as a Potential Cardioprotective Agent: Understanding its Mechanisms

Introduction to Cardioprotection

  • The SIRT family and their role in metabolic health
  • Decline of SIRT activity with age and the investigation into NAD+ precursors
  • NMN and NR as orally bioavailable NAD+ precursors undergoing clinical trials

Importance of SIRT1 in Cardioprotection

  • Cardiac SIRT1's role in cardioprotective paradigms, including ischemic preconditioning
  • NMN's demonstrated cardioprotective effects in a mouse model of ischemia-reperfusion (IR) injury
  • Attribution of NMN's activity to SIRT1 stimulation, but limited knowledge of other mechanisms

Investigating NMN-Induced Cardioprotection in Mice

  • Use of wild-type and Sirt3-deficient mice in the study
  • Langendorff constant flow mode for heart perfusion
  • Delivery of NMN, splitomicin (SIRT1 inhibitor), and vehicle during the experiment
  • Monitoring cardiac function digitally using a pressure transducer
  • Determination of heart infarction using tetrazolium chloride staining
  • Metabolomic and glycolytic flux measurements for analysis
  • Various tests and assays performed to gather data

Findings of the Study

  • NMN-induced cardioprotection not affected by SIRT1 inhibition
  • Lysine deacetylation occurred in the mitochondria, suggesting involvement of SIRT3
  • Absence of NMN-induced cardioprotection in Sirt3-deficient hearts due to enhanced baseline injury
  • NMN stimulation of cardiac glycolysis and cytosolic acidification in primary cardiomyocytes
  • Importance of glycolytic stimulation for NMN-induced cardioprotection
  • NMN's potential multiple mechanisms of action, including SIRT1, SIRT3, glycolytic stimulation, and acidosis

Implications and Considerations

  • Linking NMN-induced glycolysis to enhanced ATP synthesis for cardioprotection
  • Understanding the role of acidosis and lysine deacetylation in NMN-induced cardioprotection
  • Caution urged in dietary NMN and NR supplementation due to potential negative effects

Supplementary Material and Funding

  • Availability of additional material supplementing the main content
  • Grants from the US National Institutes of Health supporting the study
  • Acknowledgment of technical support and absence of conflicts of interest

Final Remarks

  • Status of the provided manuscript as an unedited version accepted for publication
  • Mention of upcoming processes before final publication and potential for errors
  • Application of legal disclaimers to the manuscript

Title of paper: Cardioprotection by nicotinamide mononucleotide (NMN): Involvement of glycolysis and acidic pH

Author(s): Nadtochiy SM, Wang YT, Nehrke K, Munger J, Brookes PS.

Year published: 2018

Published in: J Mol Cell Cardiol

Original article can be found here.

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