Neuroprotective effect of rLosac on supplement-deprived mouse cultured cortical neurons involves maintenance of monocarboxylate transporter MCT2 protein levels.

Details

Serval ID
serval:BIB_7BD6C10999BE
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Neuroprotective effect of rLosac on supplement-deprived mouse cultured cortical neurons involves maintenance of monocarboxylate transporter MCT2 protein levels.
Journal
Journal of neurochemistry
Author(s)
Alvarez-Flores M.P., Hébert A., Gouelle C., Geller S., Chudzinski-Tavassi A.M., Pellerin L.
ISSN
1471-4159 (Electronic)
ISSN-L
0022-3042
Publication state
Published
Issued date
01/2019
Peer-reviewed
Oui
Volume
148
Number
1
Pages
80-96
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
The recombinant Lonomia obliqua Stuart-factor activator (rLosac) is a recombinant hemolin which belongs to the immunoglobulin superfamily of cell adhesion molecules. It is capable of inducing pro-survival activity in serum-deprived human umbilical vein endothelial cells (HUVECs) and fibroblasts by increasing mitochondrial metabolism. We hypothesize that it could promote neuronal survival by acting on neuroenergetics. Our study reveals that treatment of primary mouse cortical neurons cultured in neurobasal medium lacking B27 supplement with rLosac led to an enhancement of cell viability in a time- and concentration-dependent manner. In parallel, preserved or enhanced phosphorylation of Akt, p44, and p42 MAPK, as well as mTOR was observed following treatment with rLosac. During deprivation, as assessed by western blot and qRT-PCR, protein and mRNA expression of MCT2 (the predominant neuronal monocarboxylate transporter allowing lactate use as an alternative energy substrate) decreased significantly in B27 supplement-deprived cortical neurons and was hardly detected after 24 h of deprivation. Interestingly, rLosac maintained MCT2 protein expression after 24 h of deprivation including at the cell surface without preventing mRNA loss. MCT2 knockdown reduced rLosac-enhanced cell viability, confirming its involvement in rLosac effect. Enhanced uptake of lactate was detected following rLosac treatment and might contribute to rLosac-enhanced viability during deprivation. In the presence of both lactate and rLosac, cell viability was higher than in the presence of lactate alone. Our observations suggest that rLosac promotes cell viability in stressed (B27 supplement-deprived) neurons by facilitating the use of lactate as energy substrate via the preservation of MCT2 protein expression. OPEN SCIENCE BADGES: This article has received a badge for *Open Materials* because it provided all relevant information to reproduce the study in the manuscript. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https://cos.io/our-services/open-science-badges/.
Keywords
MCT2, energy, hemolin, lactate, neuroprotection, rLosac
Pubmed
Create date
05/11/2018 9:13
Last modification date
21/08/2019 5:33
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