| Full text | |
| Author(s): |
Alvarez-Flores, Milyam P.
[1, 2]
;
Hebert, Audrey
[1]
;
Gouelle, Cathy
[1]
;
Geller, Sarah
[1]
;
Chudzinski-Tavassi, Ana M.
[2]
;
Pellerin, Luc
[1, 3]
Total Authors: 6
|
| Affiliation: | [1] Univ Lausanne, Dept Physiol, 7 Rue Bugnon, CH-1005 Lausanne - Switzerland
[2] Butantan Inst, CENTD, Lab Mol Biol, Sao Paulo - Brazil
[3] Univ Bordeaux, Ctr Resonance Magnet Syst Biol, CNRS UMR5536, LabEx TRAIL IBIO, Bordeaux - France
Total Affiliations: 3
|
| Document type: | Journal article |
| Source: | Journal of Neurochemistry; v. 148, n. 1, p. 80-96, JAN 2019. |
| Web of Science Citations: | 1 |
| 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 24h of deprivation. Interestingly, rLosac maintained MCT2 protein expression after 24h 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. (AU) | |
| FAPESP's process: | 13/07467-1 - CeTICS - Center of Toxins, Immune-Response and Cell Signaling |
| Grantee: | Hugo Aguirre Armelin |
| Support Opportunities: | Research Grants - Research, Innovation and Dissemination Centers - RIDC |
| FAPESP's process: | 15/50040-4 - Rational approach for searching molecular targets involved in inflammatory events and cell survival |
| Grantee: | Ana Marisa Chudzinski-Tavassi |
| Support Opportunities: | Research Grants - Research Centers in Engineering Program |