RESUMO
To survive, cells must rapidly repair (seal) plasmalemmal damage. Cytosolic oxidation has been shown to increase cell survival in some cases and produce cell death in other protocols. An antioxidant (melatonin; Mel) has been reported to decrease the probability of sealing plasmalemmal damage. Here we report that plasmalemmal damage produces cytosolic oxidation, as assayed by methylene blue (MB) color change in rat B104 hippocampal cells. Plasmalemmal sealing is affected by duration of Ca²âº deprivation and length of exposure to, and concentration of, oxidizing agents such as H2O2 and thimerosal (TH). Cytosolic oxidation by 10 µM to 50 mM H2O2 or 100 µM to 2 mM TH increases the probability of Ca²âº-dependent plasmalemmal sealing, whereas higher concentrations of H2O2 decrease sealing probability and also damage uninjured cells. We also show that antioxidants (Mel, MB) or reducing agents (dithiothreitol) decrease sealing. Proteins, such as protein kinase A, SNAP-25, synaptobrevin, and N-ethylmaleimide-sensitive factor (previously reported to enhance sealing in other pathways), also enhance sealing in this oxidation pathway. In brief, our data show that plasmalemmal damage produces cytosolic oxidation that increases the probability of plasmalemmal sealing, which is strongly correlated with cell survival in other studies. Our results may provide new insights into the etiology and treatment of oxidation-dependent neurodegenerative disorders, such as Parkinson's, Huntington's, and Alzheimer's diseases.
Assuntos
Axotomia , Membrana Celular/fisiologia , Citosol/fisiologia , Neuritos/metabolismo , Cicatrização/fisiologia , Animais , Antioxidantes/farmacologia , Cálcio/metabolismo , Linhagem Celular Tumoral , Membrana Celular/efeitos dos fármacos , Citosol/efeitos dos fármacos , Relação Dose-Resposta a Droga , Interações Medicamentosas , Peróxido de Hidrogênio/farmacologia , Neuritos/efeitos dos fármacos , Neuroblastoma/patologia , Oxidantes/farmacologia , Oxirredução/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Ratos , Fatores de Tempo , Cicatrização/efeitos dos fármacosRESUMO
Tensions between the world of science and the world of law may arise because of their differing viewpoints and philosophies. Disagreements may center around such questions as what constitutes proof, around human behavior, and around the use of the insanity defense in criminal cases. The just deserts model is examined and is criticized as being harsh and possibly unrealistic in today's society.
