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NEUROVASCULAR MEDICINE - Pursuing Cellular Longevity for Healthy Aging Part 10

Các tế bào soma của người bình thường đều có một đời sống có giới hạn. Thông thường tế bào chết đi sau 40-60 chu kì sao chép. Thời gian sống của mỗi tế bào được quyết định về di truyền học bởi hai hệ thống độc lập với nhau. | 528 NOVEL CELLULAR PATHWAYS the characteristic changes of the early phase of diabetic retinopathy in streptozotocin-induced diabetic rats. These observations suggest that SDH-mediated conversion of sorbitol into fructose and the resultant ROS generation may play a role in the pathogenesis of diabetic retinopathy. Since fructose is a stronger glycating agent than glucose intracellular AGEs formation via the SDH pathway might be involved in glucose toxicity to retinal pericytes Rosen Nawroth King et al. 2001 . There is a growing body of evidence that generation of ROS is increased in diabetes. High glucose concentrations via various mechanisms such as glucose autoxidation increased the production of AGEs activation of PKC and stimulation of the polyol pathway and it enhanced ROS generation Rosen Nawroth King et al. 2001 Bonnefont-Rousselot 2002 . Increased ROS generation has been found to regulate vascular inflammation altered gene expression of growth factors and cytokines and platelet and macrophage activation thus playing a central role in the pathogenesis of diabetic vascular complications Yamagishi Edelstein Du et al. 2001 Yamagishi Edelstein Du et al. 2001 Yamagishi Okamoto Amano et al. 2002 Spitaler Graier 2002 Yamagishi Inagaki Amano et al. 2002 Yamagishi S Amano S Inagaki et al. 2003 . Further we have recently found that high glucose-induced mitochondrial overproduction of superoxide serves as a causal link between elevated glucose and hyperglycemic vascular damage in ECs Nishikawa Edelstein Du et al. 2000 Brownlee 2001 . Normalizing levels of mitochondrial ROS prevent glucose-induced formation of AGEs activation of PKC sorbitol accumulation and NF-kB activation. These observations suggest that the three main mechanisms implicated in the pathogenesis of diabetic vascular complications might reflect a single hyperglycemia-induced process thus providing a novel therapeutic target for diabetic angiopathies. Recently Hammes et al. Hammes Du Edelstein et al. 2003