Lipoic acid protects C6 cells against ammonia exposure through Naâº-Kâº-Clâ» co-transporter and PKC pathway.
Toxicol In Vitro
; 27(7): 2041-8, 2013 Oct.
Article
in En
| MEDLINE
| ID: mdl-23880158
ABSTRACT
Astrocytes play an essential role in the central nervous system (CNS) homeostasis. They providing metabolic support and protecting against oxidative stress and glutamatergic excitotoxicity. Glutamate uptake, an electrogenic function, is driven by cation gradients and the Naâº-Kâº-Clâ» co-transporter (NKCC1) carries these ions into and out of the cell. Elevated concentrations of ammonia in the brain lead to cerebral dysfunction. Ammonia toxicity can be mediated by an excitotoxic mechanism, oxidative stress and ion discharged. Astrocytes also convert excess ammonia and glutamate into glutamine, via glutamine synthetase (GS). Lipoic acid (LA) is a modulator of the cellular redox status potentially beneficial in neurodegenerative diseases. In this study, we investigated the effect of LA on glial parameters, in C6 cells exposed to ammonia. Ammonia increased S100B secretion and decreased glutamate uptake, GS activity and glutathione (GSH) content. LA was able to prevent these effects. LA exerts its protective effect on glutamate uptake and S100B secretion via mechanisms dependent of NKCC1 and PKC. These findings show that LA is able to modulate glial function impairments by ammonia in vitro, indicating a potential therapeutic agent to improve glutamatergic metabolism and oxidative stress against hyperammonemia.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Protein Kinase C
/
Astrocytes
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Thioctic Acid
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Oxidative Stress
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Neuroprotective Agents
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MAP Kinase Signaling System
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Solute Carrier Family 12, Member 2
Language:
En
Journal:
Toxicol In Vitro
Journal subject:
TOXICOLOGIA
Year:
2013
Document type:
Article
Affiliation country:
Brazil