| Title : Alpha7 nicotinic receptor activation protects against oxidative stress via heme-oxygenase I induction - Navarro_2015_Biochem.Pharmacol_97(4)_473 |
| Author(s) : Navarro E , Buendia I , Parada E , Leon R , Jansen-Duerr P , Pircher H , Egea J , Lopez MG |
| Ref : Biochemical Pharmacology , 97 :473 , 2015 |
| Abstract : Subchronic oxidative stress and inflammation are being increasingly implicated in the pathogenesis of numerous diseases, such as Alzheimer's or Parkinson's disease. This study was designed to evaluate the potential protective role of alpha7 nicotinic receptor activation in an in vitro model of neurodegeneration based on subchronic oxidative stress. Rat organotypic hippocampal cultures (OHCs) were exposed for 4 days to low concentration of lipopolysaccharide (LPS) and the complex III mitochondrial blocker, antimycin-A. Antimycin-A (0.1muM) and lipopolysaccharide (1ng/ml) caused low neurotoxicity on their own, measured as propidium iodide fluorescence in CA1 and CA3 regions. However, their combination (LPS/AA) caused a greater detrimental effect, in addition to mitochondrial depolarization, overproduction of reactive oxygen species (ROS) and Nox4 overexpression. Antimycin-A per se increased ROS and mitochondrial depolarization, although these effects were significantly higher when combined with LPS. More interesting was the finding that exposure of OHCs to the combination of LPS/AA triggered aberrant protein aggregation, measured as thioflavin S immunofluorescence. The alpha7 nicotinic receptor agonist, PNU282987, prevented the neurotoxicity and the pathological hallmarks observed in the LPS/AA subchronic toxicity model (oxidative stress and protein aggregates); these effects were blocked by alpha-bungarotoxin and tin protoporphyrin, indicating the participation of alpha7 nAChRs and heme-oxygenase I induction. In conclusion, subchronic exposure of OHCs to low concentration of antimycin-A plus LPS reproduced pathological features of neurodegenerative disorders. alpha7 nAChR activation ameliorated these alterations by a mechanism involving heme-oxygenase I induction. |
| ESTHER : Navarro_2015_Biochem.Pharmacol_97(4)_473 |
| PubMedSearch : Navarro_2015_Biochem.Pharmacol_97(4)_473 |
| PubMedID: 26212551 |
Navarro E, Buendia I, Parada E, Leon R, Jansen-Duerr P, Pircher H, Egea J, Lopez MG (2015)
Alpha7 nicotinic receptor activation protects against oxidative stress via heme-oxygenase I induction
Biochemical Pharmacology
97 :473
Navarro E, Buendia I, Parada E, Leon R, Jansen-Duerr P, Pircher H, Egea J, Lopez MG (2015)
Biochemical Pharmacology
97 :473