9 research outputs found
Variation of plasma cortisol levels in patients with depression after treatment with bilateral electroconvulsive therapy
The antiapoptotic effect of guanosine is mediated by the activation of the PI 3-kinase/AKT/PKB pathway in cultured rat astrocytes
10nonenoneDI IORIO P.; BALLERINIP.; TRAVERSA U.; NICOLETTI F.; D'ALIMONTE I.; KLEYWEGT S.; WERSTIUK E.S.; RATHBONE M.P.; CACIAGLI F.; CICCARELLI R.DI IORIO, P.; Ballerinip, ; Traversa, Ugo; Nicoletti, F.; D'Alimonte, I.; Kleywegt, S.; Werstiuk, E. S.; Rathbone, M. P.; Caciagli, F.; Ciccarelli, R
The antiapoptotic effect of guanosine is mediated by the activation of the PI 3-kinase/AKT/PKB pathway in cultured rat astrocytes.
Guanosine has many trophic effects in the CNS, including the stimulation of neurotrophic factor synthesis and release by astrocytes, which protect neurons against excitotoxic death. Therefore, we questioned whether guanosine protected astrocytes against apoptosis induced by staurosporine. We evaluated apoptosis in cultured rat brain astrocytes, following exposure (3 h) to 100 nM staurosporine by acridine orange staining or by oligonucleosome, or caspase-3 ELISA assays. Staurosporine promoted apoptosis rapidly, reaching its maximal effect (approximately 10-fold over basal apoptotic values) in 18-24 h after its administration to astrocytes. Guanosine, added to the culture medium for 4 h, starting from 1 h prior to staurosporine, reduced the proportion of apoptotic cells in a concentration-dependent manner. The IC50 value for the inhibitory effect of guanosine is 7.5 x 10(-5) M. The protective effect of guanosine was not affected by inhibiting the nucleoside transporters by propentophylline, or by the selective antagonists of the adenosine A1 or A2 receptors (DPCPX or DMPX), or by an antagonist of the P2X and P2Y purine receptors (suramin). In contrast, pretreatment of astrocytes with pertussis toxin, which uncouples Gi-proteins from their receptors, abolished the antiapoptotic effect of guanosine. The protective effect of guanosine was also reduced by pretreatment of astrocytes with inhibitors of the phosphoinositide 3-kinase (PI3K; LY294002, 30 microM) or the MAPK pathway (PD98059, 10 microM). Addition of guanosine caused a rapid phosphorylation of Akt/PKB, and glycogen synthase kinase-3beta (GSK-3beta) and induced an upregulation of Bcl-2 mRNA and protein expression. These data demonstrate that guanosine protects astrocytes against staurosporine-induced apoptosis by activating multiple pathways, and these are mediated by a Gi-protein-coupled putative guanosine receptor
P2X7 receptor activation in rat brain cultured astrocytes increases the biosynthetic release of cysteinyl leukotrienes.
Hydralazine targets cAMP-dependent protein kinase leading to sirtuin1/5 activation and lifespan extension in C. elegans
ExercĂcio fĂsico, receptores β-adrenĂ©rgicos e resposta vascular Physical exercise, β-adrenergic receptors, and vascular response
O exercĂcio aerĂłbio promove efeitos benĂ©ficos na prevenção e tratamento de doenças como hipertensĂŁo arterial, aterosclerose, insuficiĂŞncia venosa e doença arterial perifĂ©rica. Os receptores β-adrenĂ©rgicos estĂŁo presentes em várias cĂ©lulas. No sistema cardiovascular, promovem inotropismo e cronotropismo positivo cardĂaco e relaxamento vascular. Embora os efeitos do exercĂcio tenham sido investigados em receptores cardĂacos, estudos focados nos vasos sĂŁo escassos e controversos. Esta revisĂŁo abordará os efeitos do exercĂcio fĂsico sobre os receptores β-adrenĂ©rgicos vasculares em modelos animais e humanos e os mecanismos celulares envolvidos na resposta relaxante. Em geral, os estudos mostram resultantes conflitantes, onde observam diminuição, aumento ou nenhum efeito do exercĂcio fĂsico sobre a resposta relaxante. Assim, os efeitos do exercĂcio na sensibilidade β-adrenĂ©rgica vascular merecem maior atenção, e os resultados mostram que a área de fisiopatologia vascular Ă© um campo aberto para a descoberta de novos compostos e avanços na prática clĂnica.<br>Aerobic exercise promotes beneficial effects on the prevention and treatment of diseases such as arterial hypertension, atherosclerosis, venous insufficiency, and peripheral arterial disease. β-adrenergic receptors are present in a variety of cells. In the cardiovascular system, β-adrenergic receptors promote positive inotropic and chronotropic response and vasorelaxation. Although the effect of exercise training has been largely studied in the cardiac tissue, studies focused on the vascular tissue are rare and controversial. This review examines the data from studies using animal and human models to determine the effect of physical exercise on the relaxing response mediated by β-adrenergic receptors as well as the cellular mechanisms involved in this response. Studies have shown reduction, increase, or no effect of physical exercise on the relaxing response mediated by β-adrenergic receptors. Thus, the effects of exercise on the vascular β-adrenergic sensitivity should be more deeply investigated. Furthermore, the physiopathology of the vascular system is an open field for the discovery of new compounds and advances in the clinical practice