Scientific Reports (Sep 2021)

Role of pyruvate in maintaining cell viability and energy production under high-glucose conditions

  • Hideji Yako,
  • Naoko Niimi,
  • Ayako Kato,
  • Shizuka Takaku,
  • Yasuaki Tatsumi,
  • Yasumasa Nishito,
  • Koichi Kato,
  • Kazunori Sango

DOI
https://doi.org/10.1038/s41598-021-98082-w
Journal volume & issue
Vol. 11, no. 1
pp. 1 – 17

Abstract

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Abstract Pyruvate functions as a key molecule in energy production and as an antioxidant. The efficacy of pyruvate supplementation in diabetic retinopathy and nephropathy has been shown in animal models; however, its significance in the functional maintenance of neurons and Schwann cells under diabetic conditions remains unknown. We observed rapid and extensive cell death under high-glucose (> 10 mM) and pyruvate-starved conditions. Exposure of Schwann cells to these conditions led to a significant decrease in glycolytic flux, mitochondrial respiration and ATP production, accompanied by enhanced collateral glycolysis pathways (e.g., polyol pathway). Cell death could be prevented by supplementation with 2-oxoglutarate (a TCA cycle intermediate), benfotiamine (the vitamin B1 derivative that suppresses the collateral pathways), or the poly (ADP-ribose) polymerase (PARP) inhibitor, rucaparib. Our findings suggest that exogenous pyruvate plays a pivotal role in maintaining glycolysis–TCA cycle flux and ATP production under high-glucose conditions by suppressing PARP activity.