RT Journal Article
T1 Alpha7 nicotinic receptor activation protects against oxidative stress via heme-oxygenase I induction
A1 Navarro González De Mesa, Elisa
A1 Buendía, Izaskun
A1 Parada, Esther
A1 León Martínez, Rafael
A1 Jansen-Duerr, Pidder
A1 Pircher, Haymo
A1 Egea, Javier
A1 García López, Manuela
AB 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 α7 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 (0.1μM) 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 α7 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 α-bungarotoxin and tin protoporphyrin, indicating the participation of α7 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. α7 nAChR activation ameliorated these alterations by a mechanism involving heme-oxygenase I induction.
PB Elsevier
SN 0006-2952
YR 2015
FD 2015
LK https://hdl.handle.net/20.500.14352/93273
UL https://hdl.handle.net/20.500.14352/93273
LA eng
NO Navarro E, Buendia I, Parada E, León R, Jansen-Duerr P, Pircher H, Egea J, Lopez MG. Alpha7 nicotinic receptor activation protects against oxidative stress via heme-oxygenase I induction. Biochem Pharmacol. 2015 Oct 15;97(4):473-481. doi: 10.1016/j.bcp.2015.07.022
DS Docta Complutense
RD 15 dic 2025