PMID- 26592660
OWN - NLM
STAT- MEDLINE
DCOM- 20160506
LR  - 20181113
IS  - 1873-2968 (Electronic)
IS  - 0006-2952 (Print)
IS  - 0006-2952 (Linking)
VI  - 99
DP  - 2016 Jan 1
TI  - Lactate's effect on human neuroblastoma cell bioenergetic fluxes.
PG  - 88-100
LID - S0006-2952(15)00711-X [pii]
LID - 10.1016/j.bcp.2015.11.002 [doi]
AB  - 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 beta (PGC-1beta), Akt, 
      mammalian target of rapamycin (mTOR), and forkhead box protein O1 (FOXO1). mRNA 
      levels for PGC-1beta, 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.
CI  - Copyright (c) 2015 Elsevier Inc. All rights reserved.
FAU - E, Lezi
AU  - E L
AD  - Department of Physical Therapy and Rehabilitation Sciences, University of Kansas 
      Medical Center, Kansas City, KS, USA; Department of Neurology, University of 
      Kansas Medical Center, Kansas City, KS, USA.
FAU - Swerdlow, Russell H
AU  - Swerdlow RH
AD  - Department of Neurology, University of Kansas Medical Center, Kansas City, KS, 
      USA; Department of Molecular and Integrative Physiology, University of Kansas 
      Medical Center, Kansas City, KS, USA; Department of Biochemistry and Molecular 
      Biology, University of Kansas Medical Center, Kansas City, KS, USA; University of 
      Kansas Alzheimer's Disease Center, University of Kansas Medical Center, Kansas 
      City, KS, USA. Electronic address: rswerdlow@kumc.edu.
LA  - eng
GR  - P30 AG035982/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20151121
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 33X04XA5AT (Lactic Acid)
SB  - IM
MH  - Cell Line, Tumor
MH  - Dose-Response Relationship, Drug
MH  - Energy Metabolism/*drug effects/*physiology
MH  - Humans
MH  - Lactic Acid/*pharmacology
MH  - Neuroblastoma/*metabolism
PMC - PMC4706500
MID - NIHMS738642
OTO - NOTNLM
OT  - Bioenergetics
OT  - Glycolysis
OT  - Lactate
OT  - Mitochondrial respiration
OT  - SH-SY5Y
COIS- No conflicts of interest, financial or otherwise, are declared by the authors.
EDAT- 2015/11/26 06:00
MHDA- 2016/05/07 06:00
PMCR- 2017/01/01
CRDT- 2015/11/24 06:00
PHST- 2015/08/19 00:00 [received]
PHST- 2015/11/02 00:00 [accepted]
PHST- 2015/11/24 06:00 [entrez]
PHST- 2015/11/26 06:00 [pubmed]
PHST- 2016/05/07 06:00 [medline]
PHST- 2017/01/01 00:00 [pmc-release]
AID - S0006-2952(15)00711-X [pii]
AID - 10.1016/j.bcp.2015.11.002 [doi]
PST - ppublish
SO  - Biochem Pharmacol. 2016 Jan 1;99:88-100. doi: 10.1016/j.bcp.2015.11.002. Epub 
      2015 Nov 21.