(C) 2013 Elsevier Inc. All rights reserved.”
“Nitric oxide (NO), physical exercise and/or antidepressant drugs, through the increased release of norepinephrine and brain-derived neurotrophic factor (BDNF), have been shown to exert profound protective, pro-survival effects on neurons otherwise compromised selleck inhibitor by injury, disease, prolonged stress, and subsequent depression in vivo. We sought, therefore, to evaluate such survival and neuroprotection in hippocampal neurons in culture, which, in an analogous model of in vivo cellular stress, was deprived of several vital nutrients. We assessed pro-survival outcomes following the application of norepinephrine or the noradrenergic partial

agonist, clonidine, a general nitric ACY-738 chemical structure oxide synthase inhibitor and NO donor, using a cell survival assay and quantitative Western blotting of the survival signaling molecules, BDNF, P-CREB, P-Akt, and P-MAPK in hippocampal neuronal lysates. We demonstrate that norepinephrine, clonidine, the NO donor and various combinations of these drugs increased cell survival and the immunoreactivity of the four survival signaling molecules in the face of nutrient deprivation stress, whereas the NO synthase inhibitor, and each of several survival

signaling pathway inhibitors all decreased cell survival even below that of controls without nutrient supplementation. These results demonstrate that conditions that make cells vulnerable to environmental/toxic insult can be offset by norepinephrine and its related drugs or by NO donors and exacerbated by drugs that specifically inhibit a key survival signaling pathway. These results indicate that pharmacological intervention can promote neuroprotection and survival signaling in the face of nutrient withdrawal, but that this may require that several pathways remain

intact. (C) 2010 Elsevier B.V. All rights reserved.”
“In this study, we examined the relative efficacies of alpha-tocopherol, N-acetyl-serotonin, and melatonin in reducing ascorbate-Fe(2+) lipid peroxidation (LPO) of rat testicular microsomes and mitochondria. Special attention was paid to the changes produced on click here the highly polyunsaturated fatty acids (PUFAs) C20:4 n6 and C22:5 n6. The LPO of testicular microsomes or mitochondria produced a significant decrease of C20:4 n6 and C22:5 n6. Both long-chain PUFAs were protected when the antioxidants were incorporated either in microsomes or mitochondria. By comparison of the IC50 values obtained between alpha-tocopherol and both indolamines, it was observed that alpha-tocopherol was the most efficient antioxidant against the LPO induced by ascorbate-Fe(2+) under experimental conditions in vitro, IC50 values from the inhibition of alpha-tocopherol on the chemiluminescence were higher in microsomes (0.14 mM) than in mitochondria (0.08 mM).