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

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 diabe...

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Autores principales:	Hideji Yako, Naoko Niimi, Ayako Kato, Shizuka Takaku, Yasuaki Tatsumi, Yasumasa Nishito, Koichi Kato, Kazunori Sango
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a6f9d58fa8e244a9b2cbca3a21ee51ce
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spelling	oai:doaj.org-article:a6f9d58fa8e244a9b2cbca3a21ee51ce2021-12-02T18:48:03ZRole of pyruvate in maintaining cell viability and energy production under high-glucose conditions10.1038/s41598-021-98082-w2045-2322https://doaj.org/article/a6f9d58fa8e244a9b2cbca3a21ee51ce2021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-98082-whttps://doaj.org/toc/2045-2322Abstract 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.Hideji YakoNaoko NiimiAyako KatoShizuka TakakuYasuaki TatsumiYasumasa NishitoKoichi KatoKazunori SangoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-17 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hideji Yako Naoko Niimi Ayako Kato Shizuka Takaku Yasuaki Tatsumi Yasumasa Nishito Koichi Kato Kazunori Sango Role of pyruvate in maintaining cell viability and energy production under high-glucose conditions
description	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.
format	article
author	Hideji Yako Naoko Niimi Ayako Kato Shizuka Takaku Yasuaki Tatsumi Yasumasa Nishito Koichi Kato Kazunori Sango
author_facet	Hideji Yako Naoko Niimi Ayako Kato Shizuka Takaku Yasuaki Tatsumi Yasumasa Nishito Koichi Kato Kazunori Sango
author_sort	Hideji Yako
title	Role of pyruvate in maintaining cell viability and energy production under high-glucose conditions
title_short	Role of pyruvate in maintaining cell viability and energy production under high-glucose conditions
title_full	Role of pyruvate in maintaining cell viability and energy production under high-glucose conditions
title_fullStr	Role of pyruvate in maintaining cell viability and energy production under high-glucose conditions
title_full_unstemmed	Role of pyruvate in maintaining cell viability and energy production under high-glucose conditions
title_sort	role of pyruvate in maintaining cell viability and energy production under high-glucose conditions
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/a6f9d58fa8e244a9b2cbca3a21ee51ce
work_keys_str_mv	AT hidejiyako roleofpyruvateinmaintainingcellviabilityandenergyproductionunderhighglucoseconditions AT naokoniimi roleofpyruvateinmaintainingcellviabilityandenergyproductionunderhighglucoseconditions AT ayakokato roleofpyruvateinmaintainingcellviabilityandenergyproductionunderhighglucoseconditions AT shizukatakaku roleofpyruvateinmaintainingcellviabilityandenergyproductionunderhighglucoseconditions AT yasuakitatsumi roleofpyruvateinmaintainingcellviabilityandenergyproductionunderhighglucoseconditions AT yasumasanishito roleofpyruvateinmaintainingcellviabilityandenergyproductionunderhighglucoseconditions AT koichikato roleofpyruvateinmaintainingcellviabilityandenergyproductionunderhighglucoseconditions AT kazunorisango roleofpyruvateinmaintainingcellviabilityandenergyproductionunderhighglucoseconditions
_version_	1718377641964208128

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

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