Lactate's effect on human neuroblastoma cell bioenergetic fluxes. Biochem Pharmacol 2016 Jan 01;99:88-100
Date
11/26/2015Pubmed ID
26592660Pubmed Central ID
PMC4706500DOI
10.1016/j.bcp.2015.11.002Scopus ID
2-s2.0-84951794583 (requires institutional sign-in at Scopus site) 10 CitationsAbstract
Lactate, once considered a metabolic dead-end, has been recently proposed to support neuron bioenergetics. To better understand how lactate specifically influences cell energy metabolism, we studied the effects of lactate supplementation on SH-SY5Y human neuroblastoma cell bioenergetic fluxes. Lactate supplementation increased cell respiration, there was no change in respiratory coupling efficiency, and lactate itself appeared to directly support the respiratory flux increase. Conversely, lactate supplementation reduced the glycolysis flux. This apparent pro-aerobic shift in the respiration:glycolysis ratio was accompanied by post-translational modifications and compartmental redistributions of proteins that respond to and modify bioenergetic fluxes, including cAMP-response element binding protein (CREB), p38 mitogen-activated protein kinases (p38 MAPK), AMP-activated protein kinase (AMPK), peroxisome-proliferator activated receptor gamma coactivator 1 β (PGC-1β), Akt, mammalian target of rapamycin (mTOR), and forkhead box protein O1 (FOXO1). mRNA levels for PGC-1β, nuclear respiratory factor 1 (NRF1), and cytochrome c oxidase subunit 1 (COX1) increased. Some effects depended on the direct presence of lactate, while others were durable and evident several hours after lactate was removed. We conclude lactate can be used to manipulate cell bioenergetics.
Author List
E L, Swerdlow RHAuthor
Lezi E PhD Assistant Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Cell Line, TumorDose-Response Relationship, Drug
Energy Metabolism
Humans
Lactic Acid
Neuroblastoma
