The mechanisms responsible for neuroprotective capacity of arylpiperazine dopaminergic ligands against cell death induced by sodium nitroprusside

A group of sixteen arylpiperazines had been previously synthesized and evaluated for atypical antipsychotic activity. Here we examined these compounds for their neuroprotective capacity. The affinity and agonist/antagonist action of the arylpiperazines at dopamine hD(2S) receptors were determined in vitro on membranes from stably transfected CHO-hD(2S) cell line. The assays for cell viability and antioxidative capacity (total glutathione and total superoxide dismutase activity), amount of nitric oxide and superoxide radicals, as well as influence on prosurvival pathways (Akt and ERK), were performed on the human neuroblastoma cell line SH-SY5Y. Cell death was induced by oxidative or nitrosative stress, or by growing cells in the medium deprived of serum. Only four of the arylpiperazines exhibited notable neuroprotection against cell death induced by sodium nitroprusside. Two of these arylpiperazines induced elevations of pAkt, while two other compounds reduced the levels of pErk, whereas these actions are considered to support the cell survival. The benzimidazole heteroaryl-group, that mimics catechol moiety of the dopamine molecule, might be the prerequisite structure for the neuroprotective action of these ligands. It is postulated that neuroprotection was acquired also by elevation of endogenous glutathione or total superoxide dismutase activity. (C) 2012 Elsevier B.V. All rights reserved

Gender modulates development of the metabolic syndrome phenotype in fructose-fed rats

We analyzed the effects of a fructose-rich diet (FRD) to test the assumption that the expression of metabolic syndrome phenotype is different in male and female rats. Two-way ANOVA revealed a significant effect of FRD on feeding behavior and carbohydrate/lipid metabolism. The increased caloric intake in FRD rats of both sexes was followed by a cluster of gender-specific changes typical for the metabolic syndrome. Female rats were characterized by decreased glycemia, increased triglycerides, enlarged visceral adipose tissue and increased absolute mass of liver, without changes in systolic blood pressure and insulin sensitivity. In contrast, male rats developed less disturbances in physical and biochemical characteristics, but blood pressure and insulin sensitivity were impaired by FRD. The results emphasize the detrimental effects of fructose consumption on cardiovascular risk and insulin action in males, whereas females are affected by other metabolic disturbances. These results support the idea of gender-dependent differences in the expression of the metabolic syndrome phenotype

Lymphocyte glucocorticoid receptor expression level and hormone-binding properties differ between war trauma-exposed men with and without PTSD

<p>Objective: Posttraumatic stress disorder (PTSD) has been shown to be associated with altered glucocorticoid receptor (GR) activity. We studied the expression and functional properties of the receptor in peripheral blood mononuclear cells (PBMCs) from non-traumatized healthy individuals (healthy controls; n = 85), and war trauma-exposed individuals with current PTSD (n = 113), with life-time PTSD (n = 61) and without PTSD (trauma controls; n = 88). The aim of the study was to distinguish the receptor alterations related to PTSD from those related to trauma itself or to resilience to PTSD.</p><p>Methods: Functional status of the receptor was assessed by radioligand binding and lysozyme synthesis inhibition assays. The level of GR gene expression was measured by quantitative PCR and immunoblotting.</p><p>Results: Current PTSD patients had the lowest, while trauma controls had the highest number of glucocorticoid binding sites (B-max) in PBMCs. Hormone-binding potential (B-max/K-D ratio) of the receptor was diminished in the current PTSD group in comparison to all other study groups. Correlation between B-max and K-D that normally exists in healthy individuals was decreased in the current PTSD group. Contrasting B-max data, GR protein level was lower in trauma controls than in participants with current or life-time PTSD.</p><p>Conclusions: Current PTSD is characterized by reduced lymphocyte GR hormone-binding potential and by disturbed compensation between B-max and hormone-binding affinity. Resilience to PTSD is associated with enlarged fraction of the receptor molecules capable of hormone binding, within the total receptor molecule population in PBMCs. (C) 2013 Elsevier Inc. All rights reserved.</p>