RESUMO
Advanced glycation end-products (AGEs) stimulate reactive oxygen species (ROS) generation and represent a risk factor for atherosclerosis, while their formation seems to be prevented by zinc. Metallothioneins (MT), zinc-binding proteins exert an antioxidant function by regulating intracellular zinc availability and protecting cells from ROS damages. +1245 A/G MT1A polymorphism was implicated in type 2 diabetes and in cardiovascular disease development as well as in the modulation of antioxidant response. The purpose of this study was to investigate the influence of +1245 A/G MT1A polymorphism on AGEs and ROS production and to verify the effect of zinc supplementation on plasma AGEs, zinc status parameters and antioxidant enzyme activity in relation to this SNP. One hundred and ten healthy subjects (72 ± 6 years) from the ZincAge study were supplied with zinc aspartate (10 mg/day for 7 weeks) and screened for +1245 MT1A polymorphism. +1245 MT1A G+ (Arginine) genotype showed higher plasma AGEs and ROS production in peripheral blood mononuclear cells (PBMCs) than G- (Lysine) one at the baseline. No significant changes after zinc supplementation were observed for AGEs, ROS and MT levels as well as for enzyme antioxidant activity in relation to the genotype. Among zinc status parameters, major increases were observed for the intracellular labile zinc (iZnL) and the NO-induced release of zinc in PBMCs, in G+ genotype as compared to G- one. In summary, +1245 G+ carriers showed increased plasma AGEs and ROS production in PBMCs at baseline and a higher improvement in iZnL after zinc intervention with respect to G- individuals.
RESUMO
Advanced glycation end products (AGEs) are stable end products of the Maillard reaction. Effects of food extracts are often initially analysed in cellular test systems and it is not clear how different cell culture conditions might influence the results. Therefore, we compared the effects of two models for AGE-rich food, bread crust and coffee extract (CE) on WI-38 human lung fibroblasts under different cell culture conditions (sub-confluent versus confluent cells, with and without serum). WI-38 cells responded to coffee and bread crust extract (BCE) with a rapid phosphorylation of PKB (AKT), p42/44 MAPK (ERK 1/2) and p38 MAPK, strongly depending on culture conditions. BCE resulted in increased cell numbers, whereas CE appeared to be cytotoxic. When cell numbers under all culture conditions and treatments were correlated with kinase phosphorylation, the relation between phospho-p38 MAPK and phospho-AKT represented a good, cell culture condition-independent predictor of cell survival.
Assuntos
Pão , Técnicas de Cultura de Células , Sobrevivência Celular/efeitos dos fármacos , Café , Fibroblastos/efeitos dos fármacos , Produtos Finais de Glicação Avançada , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Linhagem Celular , Células Cultivadas , Humanos , Pulmão/citologia , Pulmão/efeitos dos fármacos , Reação de Maillard , Fosforilação , Preparações de Plantas/farmacologiaRESUMO
Experimental and clinical investigations suggest that blockade of Na(+)/H(+) exchange (NHE) with cariporide provides functional protection during ischemia and reperfusion in mature hearts. The benefit on aged human myocardium is unknown. Therefore, the impact of cardiac aging on cardio-protection by cariporide after prolonged ischemia was studied in isolated myocardium of adult (
Assuntos
Envelhecimento/fisiologia , Cardiotônicos/farmacologia , Guanidinas/farmacologia , Coração/efeitos dos fármacos , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Sulfonas/farmacologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antiarrítmicos/farmacologia , Proteínas de Transporte de Cátions/antagonistas & inibidores , Proteínas de Transporte de Cátions/metabolismo , Avaliação Pré-Clínica de Medicamentos/métodos , Coração/fisiopatologia , Átrios do Coração/efeitos dos fármacos , Átrios do Coração/fisiopatologia , Humanos , Precondicionamento Isquêmico Miocárdico , Pessoa de Meia-Idade , Contração Miocárdica/efeitos dos fármacos , Técnicas de Cultura de Órgãos , Trocador 1 de Sódio-Hidrogênio , Trocadores de Sódio-Hidrogênio/antagonistas & inibidores , Trocadores de Sódio-Hidrogênio/metabolismoRESUMO
High mobility group box protein 1 (HMGB1) is a ubiquitous nuclear protein that can be actively released from the cell in certain conditions thereby mediating cytokine-like function. While nuclear HMGB1 modulates the transcriptional activity of cells, extracellular HMGB1 partially acts via binding to the receptor for advanced glycation end products (RAGE), which is highly expressed in lung tissue. Therefore, we studied the impact of food-derived advanced glycation end products (AGEs), the Maillard reaction products, on the lung expression of HMGB1. Feeding rats with AGE-rich diet, containing either bread crust or coffee beverage, resulted in an upregulation of HMGB1 mRNA and protein especially in those animals receiving bread crust diet. The expression of RAGE was not influenced. Moreover, we revealed a positive correlation between an increased lung AGE level and HMGB1 protein expression in both animal groups receiving either bread crust or coffee extract but not in the control group. In contrast, the ageing-related AGE accumulation was not associated with an increased level of HMGB1 protein in lung tissue from senescent (100 wk) compared to young-adult (24 wk) rats. Our data suggest a physiological role of food- but not ageing-associated AGEs in the regulation of the HMGB1 expression in lung.