alpha-Glycerylphosphorylethanolamine rescues astrocytes from mitochondrial impairment and oxidative stress induced by amyloid beta-peptides.
The present work shows that alpha-glycerylphosphorylethanolamine (alpha-GPE) is effective in recovering astrocytes from mitochondrial membrane integrity and potential derangement and cellular oxidative stress that occur under amyloid beta-peptides-induced reactive gliosis.alpha-Glycerylphosphorylethanolamine (alpha-GPE), a new compound with nootropic properties, known to improve in vivo the learning and memory processes, has been tested for its protective properties on an in vitro model of degeneration. Rat primary astrocytic cultures treated with two amyloid-derived peptides, Abeta((1-40)) and Abeta(3(pE)-42), showed a marked reduction of the mitochondrial redox activity and membrane potential, together with an increase of oxidative species production. Plasma membrane lipid peroxidation (LPO) as well as generation of peroxides is greatly increased under Abeta-peptides toxicity. These features, typical of the reactive gliosis that accompanies neuronal degeneration, were readily recovered by pretreatment with alpha-GPE. alpha-GPE, likely improving the fluidity of cell membrane, has the potential to recover astrocytes from the general redox derangement induced by different amyloid fragments and possibly to protect from inflammation, gliosis and neurodegeneration. This is the first evidence of an antioxidant effect of the ethanolamine derivative on a rat model of chronic gliosis.
Pharmacology and Neuroscience (IST), National Cancer Research Institute (IST), c/o Advanced Biotechnology Center (CBA), L.go R. Benzi 10, 16132, Genova, Italy.
M
M
Bisaglia
V
V
Venezia
M
M
Biglieri
C
C
Russo
F
F
Mancini
C
C
Milanese
G
G
Schettini
D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects*; D002462:Cell Membrane / Q000187:drug effects / Q000648:ultrastructure; D002478:Cells, Cultured; D005911:Gliosis / Q000139:chemically induced / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008560:Membrane Fluidity / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D009410:Nerve Degeneration / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D010714:Phosphatidylethanolamines / Q000494:pharmacology*; D051381:Rats; D013778:Tetrazolium Salts; D013844:Thiazoles
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D010714:Phosphatidylethanolamines; D013778:Tetrazolium Salts; D013844:Thiazoles; C078592:amyloid beta-protein (1-40); C002449:glycerophosphoethanolamine; C022616:thiazolyl blue