Modulation of brain apoptosis-related proteins by the opioid antagonist naltrexone in mice.
Neuronal loss by apoptosis has been implicated in some neural pathologic disorders. Increasing evidence suggests a neuroprotective effect for opioid antagonists, such as naloxone and naltrexone, in a variety of neural damage experimental models and in the clinic. The purpose of the present study was to analyse the effects of naltrexone on the expression levels of proteins regulating the extrinsic (FasL and Fas) and the mitochondrial (Bcl-2, Bcl-xL, Bad and Bax) apoptotic pathways, as well as the active fragment of the executioner caspase-3 in the mouse brain. Western blotting showed that a single injection of naltrexone (1 mg/kg) induced a down-regulation of the pro-apototic proteins Fas, FasL, Bad and Bax. Our results suggest that naltrexone provides neuronal protection against injuries activating either mitochondrial, or death receptor-apoptotic pathways.
San-Emeterio
Estela P
EP
Departamento de Fisiología y Farmacología, Facultad de Medicina, Universidad de Cantabria, Santander, Spain.
Hurlé
María A
MA
D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis*; D053148:Caspase 3; D020169:Caspases / Q000096:biosynthesis; D053222:Fas Ligand Protein; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D009271:Naltrexone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D048069:Tumor Necrosis Factors / Q000096:biosynthesis; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis; D051025:bcl-Associated Death Protein / Q000096:biosynthesis; D019014:fas Receptor / Q000096:biosynthesis
D051017:Apoptosis Regulatory Proteins; C494820:Bad protein, mouse; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D009292:Narcotic Antagonists; D019253:Proto-Oncogene Proteins c-bcl-2; D048069:Tumor Necrosis Factors; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein; D019014:fas Receptor; D009271:Naltrexone; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases