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Volume 25
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10.3390/ijms252011089
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Article

Role of Exogenous Pyruvate in Maintaining Adenosine Triphosphate Production under High-Glucose Conditions through PARP-Dependent Glycolysis and PARP-Independent Tricarboxylic Acid Cycle

by
Hideji Yako
1,*,
Naoko Niimi
1,
Shizuka Takaku
1,
Ayako Kato
2,
Koichi Kato
2 and
Kazunori Sango
1,*
1
Diabetic Neuropathy Project, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan
2
Laboratory of Medicine, Aichi Gakuin University School of Pharmacy, Nagoya 464-8650, Japan
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2024, 25(20), 11089; https://doi.org/10.3390/ijms252011089
Submission received: 28 August 2024 / Revised: 26 September 2024 / Accepted: 14 October 2024 / Published: 15 October 2024
(This article belongs to the Special Issue Peripheral Neuropathies: Molecular Research and Novel Therapy)
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Abstract

Pyruvate serves as a key metabolite in energy production and as an anti-oxidant. In our previous study, exogenous pyruvate starvation under high-glucose conditions induced IMS32 Schwann cell death because of the reduced glycolysis–tricarboxylic acid (TCA) cycle flux and adenosine triphosphate (ATP) production. Thus, this study focused on poly-(ADP-ribose) polymerase (PARP) to investigate the detailed molecular mechanism of cell death. Rucaparib, a PARP inhibitor, protected Schwann cells against cell death and decreased glycolysis but not against an impaired TCA cycle under high-glucose conditions in the absence of pyruvate. Under such conditions, reduced pyruvate dehydrogenase (PDH) activity and glycolytic and mitochondrial ATP production were observed but not oxidative phosphorylation or the electric transfer chain. In addition, rucaparib supplementation restored glycolytic ATP production but not PDH activity and mitochondrial ATP production. No differences in the increased activity of caspase 3/7 and the localization of apoptosis-inducing factor were found among the experimental conditions. These results indicate that Schwann cells undergo necrosis rather than apoptosis or parthanatos under the aforementioned conditions. Exogenous pyruvate plays a pivotal role in maintaining the flux in PARP-dependent glycolysis and the PARP-independent TCA cycle in Schwann cells under high-glucose conditions.
Keywords: exogenous pyruvate; high-glucose; Schwann cells; cell death; PARP; glycolysis; tricarboxylic acid cycle; adenosine triphosphate depletion exogenous pyruvate; high-glucose; Schwann cells; cell death; PARP; glycolysis; tricarboxylic acid cycle; adenosine triphosphate depletion

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MDPI and ACS Style

Yako, H.; Niimi, N.; Takaku, S.; Kato, A.; Kato, K.; Sango, K. Role of Exogenous Pyruvate in Maintaining Adenosine Triphosphate Production under High-Glucose Conditions through PARP-Dependent Glycolysis and PARP-Independent Tricarboxylic Acid Cycle. Int. J. Mol. Sci. 2024, 25, 11089. https://doi.org/10.3390/ijms252011089

AMA Style

Yako H, Niimi N, Takaku S, Kato A, Kato K, Sango K. Role of Exogenous Pyruvate in Maintaining Adenosine Triphosphate Production under High-Glucose Conditions through PARP-Dependent Glycolysis and PARP-Independent Tricarboxylic Acid Cycle. International Journal of Molecular Sciences. 2024; 25(20):11089. https://doi.org/10.3390/ijms252011089

Chicago/Turabian Style

Yako, Hideji, Naoko Niimi, Shizuka Takaku, Ayako Kato, Koichi Kato, and Kazunori Sango. 2024. "Role of Exogenous Pyruvate in Maintaining Adenosine Triphosphate Production under High-Glucose Conditions through PARP-Dependent Glycolysis and PARP-Independent Tricarboxylic Acid Cycle" International Journal of Molecular Sciences 25, no. 20: 11089. https://doi.org/10.3390/ijms252011089

APA Style

Yako, H., Niimi, N., Takaku, S., Kato, A., Kato, K., & Sango, K. (2024). Role of Exogenous Pyruvate in Maintaining Adenosine Triphosphate Production under High-Glucose Conditions through PARP-Dependent Glycolysis and PARP-Independent Tricarboxylic Acid Cycle. International Journal of Molecular Sciences, 25(20), 11089. https://doi.org/10.3390/ijms252011089

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