Bortezomib-induced aerobic glycolysis contributes to chemotherapy-induced painful peripheral neuropathy

Molecular Pain
Taylor Ludman, Ohannes K Melemedjian

Abstract

Chemotherapy-induced painful peripheral neuropathy (CIPN) is the most common toxicity associated with widely used chemotherapeutics. CIPN is the major cause of dose reduction or discontinuation of otherwise life-saving treatment. Unfortunately, CIPN can persist in cancer survivors, which adversely affects their quality of life. Moreover, available treatments are vastly inadequate, warranting a better understanding of the biochemical and metabolic mechanisms that occur in response to chemotherapeutics which would be critical for the development of novel therapies for CIPN. Using extracellular flux analysis, this study demonstrated that the proteasome inhibitor, bortezomib, enhanced glycolysis while suppressing oxidative phosphorylation in the sensory neurons of mice. This metabolic phenotype is known as aerobic glycolysis. Bortezomib upregulated lactate dehydrogenase A and pyruvate dehydrogenase kinase 1, which consequently enhanced the production of lactate and repressed pyruvate oxidation, respectively. Moreover, lactate dehydrogenase A- and pyruvate dehydrogenase kinase 1-driven aerobic glycolysis was associated with increased extracellular acidification, augmented calcium responses, and pain in bortezomib-induced CIPN. Remar...Continue Reading

References

Jul 1, 1994·Journal of Neuroscience Methods·S R ChaplanT L Yaksh
Aug 31, 2001·Nature Neuroscience·D C Immke, E W McCleskey
Oct 13, 2001·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·D Attwell, S B Laughlin
Mar 21, 2003·Current Biology : CB·Peter Lennie
Sep 18, 2003·Nature Reviews. Cancer·Gregg L Semenza
Feb 24, 1956·Science·O WARBURG
Mar 19, 2008·Journal of the Peripheral Nervous System : JPNS·Anthony J Windebank, Wolfgang Grisold
Apr 22, 2008·Gynecologic Oncology·Jason Y Y WongImmaculata De Vivo
Sep 4, 2008·British Journal of Cancer·E D MichelakisJ R Mackey
Sep 25, 2008·American Journal of Physiology. Endocrinology and Metabolism·Sofianos AndrikopoulosJoseph Proietto
Feb 10, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Devadoss J SamuvelYan Huang
May 1, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Yo SasakiJeffrey Milbrandt
Sep 12, 2009·Science·Henrik AlleJörg R P Geiger
Sep 29, 2009·Nature Neuroscience·Tamara KingFrank Porreca
Dec 17, 2009·Proceedings of the National Academy of Sciences of the United States of America·Shanta Dhar, Stephen J Lippard
Feb 6, 2010·Proceedings of the National Academy of Sciences of the United States of America·Anne LeChi V Dang
Jul 10, 2010·PLoS Computational Biology·Biswa SenguptaJeremy E Niven
Oct 20, 2010·International Journal of Cancer. Journal International Du Cancer·Ioanna PapandreouNicholas C Denko
Jan 18, 2011·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·Wolfgang FiebigerGerhard Hamilton
Mar 16, 2011·Journal of Biomedicine & Biotechnology·Jingtao TongHoujie Liang
Jul 1, 2007·Biochemistry and Molecular Biology Education : a Bimonthly Publication of the International Union of Biochemistry and Molecular Biology·Jennifer L PowersVicky L H Bevilacqua
Jul 6, 2011·The Biochemical Journal·Martin D Brand, David G Nicholls
Dec 31, 2011·Drug Discovery Today·Neil P Jones, Almut Schulze
May 23, 2012·The Journal of Pain : Official Journal of the American Pain Society·Ying HeZaijie Jim Wang
Jan 19, 2011·ACS Chemical Neuroscience·Wei-Guang Li, Tian-Le Xu
Aug 7, 2012·PloS One·Kasirajan AyyanathanHerbert Weissbach
Sep 6, 2012·Experimental Neurology·H ZhengG J Bennett
Sep 27, 2012·Chemical Communications : Chem Comm·Haihua XiaoXiabin Jing
Mar 9, 2013·Cell Death & Disease·Y ZhaoM Tan

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Citations

Dec 22, 2019·Cancers·Flaminia ColuzziSebastiano Mercadante
Apr 4, 2021·International Journal of Molecular Sciences·Bernardino ClavoGustavo Marrero-Callico
Jun 19, 2021·The Ocular Surface·Jeremy Chung Bo ChiangMaria Markoulli
Jun 29, 2021·Neuroscience Letters·Timothy M Doyle, Daniela Salvemini
Sep 11, 2021·PloS One·Ravi K AnchooriRichard B S Roden
Oct 30, 2021·Frontiers in Oncology·Silvia ValtortaNicola Giuliani
Aug 24, 2020·Neuroscience Letters·Franziska Gross, Nurcan Üçeyler

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Methods Mentioned

BETA
Protein Assay
transfection

Software Mentioned

Graphpad Prism
Micro
IT
UN
ImageJ
Manager
Graph Pad
SCAN
Fiji
XF Analyzer

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