Extramitochondrial ATP as [Ca2+]m and cardiolipin content regulator.

An ATP-induced increase of [Ca2+]m in myometrium mitochondria matrix at the absence of exogenous Ca2+ was shown. An ATP-induced increase of Сa2+ efflux from mitochondria ([Сa2+]o) has also been shown. Mitochondria membranes were polarized upon incubation in both Mg2+- and Mg2+,ATP-medium. Cardiolipin (CL) content in mitochondria membranes decreased upon incubation of organelles in Mg2+,ATP-medium as compared to Mg2+-medium. It was suggested that ATP could play the role of a signaling molecule regulating the Ca2+ exchange in the mitochondria.

N-Stearoylethanolamine Inhibits Integrin-Mediated Activation, Aggregation, and Adhesion of Human Platelets.

N-stearoylethanolamine (NSE), a lipid mediator that belongs to the N-acylethanolamine (NAE) family, has anti-inflammatory, antioxidant, and membranoprotective actions. In contrast to other NAEs, NSE does not interact with cannabinoid receptors. The exact mechanism of its action remains unclear. The aim of this study is to evaluate the action of NSE on activation, aggregation, and adhesion of platelets that were chosen as a model of cellular response. Aggregation of platelets was measured to analyze the action of NSE (10-6-10-10 M) on platelet reactivity. Changes in granularity and shape of resting platelets and platelets stimulated with ADP in the presence of NSE were monitored by flow cytometry, and platelet deganulation was monitored by spectrofluorimetry. In vivo studies were performed using obese insulin-resistant rats. Binding of fibrinogen to the GPIIb/IIIa receptor was estimated using indirect ELISA and a scanning electron microscopy (SEM). It was found that NSE inhibits the activation and aggregation of human platelets. Our results suggest that NSE may decrease the activation and subsequent aggregation of platelets induced by ristocetin, epinephrine, and low doses of ADP. NSE also reduced the binding of fibrinogen to GPIIb/IIIa on activated platelets. These effects could be explained by the inhibition of platelet activation mediated by integrin receptors: the GPIb-IX-V complex for ristocetin-induced activation and GPIIb/IIIa when epinephrine and low doses of ADP were applied. The anti-platelet effect of NSE complements its anti-inflammatory effect and allows us to prioritize studies of NSE as a potent anti-thrombotic agent. SIGNIFICANCE STATEMENT: N-stearoylethanolamine (NSE) was shown to possess inhibitory action on platelet activation, adhesion, and aggregation. The mechanism of inhibition possibly involves integrin receptors. This finding complements the known anti-inflammatory effects of NSE.

AGE-RELATED MORPHO-FUNCTIONAL CHANGES IN RATS' PANCREAS UNDER HIGH-FAT DIET-INDUCED INSULIN RESISTANCE AND ITS PHARMACOLOGICAL TREATMENT.

OBJECTIVE: The aim: To determine the set of structural and functional changes in pancreatic islets (PI) of obesity-induced insulin resistant (IR) rats of different age (young and old) fed with prolonged (6 month) high-fat diet (HFD) (58% of fat) and further treatment with N-Stearoylethanolamine (NSE), a bioactive N-Acylethanolamine. PATIENTS AND METHODS: Materials and methods: Alimentary obesity-induced IR model in rats of two age groups was used to investigate the influence of age and NSE treatment on pancreas morphology (using histological, histochemical and immunohistochemical techniques) and on several biochemical parameters associated with DM onset. RESULTS: Results: The NSE administration normalized pancreas morphology which was more affected in the old IR group; the signs of inflammation, edema, fibrosis and steatosis were somehow diminished and PI area became significantly increased. The amount of the A-F-positive insulocytes increased and TUNEL-positive - decreased. Compensatory hyperplasia in the affected pancreas of both age was an important indicator of NSE stimulating effect. CONCLUSION: Conclusions: Protective effects of NSE on morpho-functional state of pancreas in HFD-induced IR rats of both age are associated not only with its anti-inflammatory, anti-oxidant and anti-dyslipidemic properties but also with activation of PI hyperplasia and ß-cells compensatory mechanisms.

N-Stearoylethanolamine suppresses the pro-inflammatory cytokines production by inhibition of NF-κB translocation.

N-Stearoylethanolamine (NSE) is a minor lipid that belongs to the N-Acylethanolamines family that mediates a wide range of biological processes. This study investigates the mechanisms of anti-inflammatory action of NSE on different model systems. Namely, we estimated the effect of NSE on inflammatory cytokines mRNA level (leukemia cells L1210), cytokines content (serum and LPS-stimulated macrophages) and nuclear translocation of NF-κB (peritoneal macrophages LPS-stimulated and isolated from rats with obesity-induced insulin resistance). The results indicated that NSE dose-dependently inhibits the IL-1 and IL-6 mRNA level in L1210 cells. Furthermore, the NSE treatment triggered a normalization of serum TNF-α level in insulin resistant rats and a reduction of medium IL-1 level in LPS-activated peritoneal macrophages. These NSE's effects were associated with the inhibition of nuclear NF-κB translocation in rat peritoneal macrophages.