Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04179 (MnSOD)
 2,777 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Defective intracellular antioxidant enzyme production (IAP) has been demonstrated in adults with diabetic nephropathy. To evaluate the effects on IAP of vitamin E administration in adolescents with type 1 diabetes and early signs of microangiopathy, 12 adolescents (aged 11-21 y; diabetes duration 10-18) were studied. Eight had retinopathy [background (four), preproliferative (three), or proliferative (one)], four had persistent microalbuminuria, and seven had both. Skin fibroblasts were obtained by biopsies and cultured in Dulbecco's modified Eagle's medium. CuZn superoxide dismutase (SOD), MnSOD, catalase (CAT), and glutathione-peroxidase (GPX) activity and mRNA expression were measured before and after 3 mo of synthetic vitamin E supplementation (600 mg twice daily); on both occasions, IAP was evaluated at different ex vivo glucose concentrations (5 and 22 mM). Ten adolescents with type 1 diabetes (aged 12-20 y) without angiopathy and eight healthy volunteers (aged 15-22 y) participated as control subjects. Vitamin E serum levels were measured throughout the study. In normal glucose concentrations, CuZnSOD, MnSOD, CAT, and GPX activity and mRNA expression were not different among the groups. In high glucose, CuZnSOD activity and mRNA increased similarly in all groups [angiopathics: 0.96 +/- 0.30 U/mg protein; 9.9 +/- 3.2 mRNA/glyceraldehyde-3-phosphate dehydrogenase). CAT and GPX activity and mRNA did not increase in high glucose only in adolescents with angiopathy (0.35 +/- 0.09; 4.2 +/- 0.1 and 0.52 +/- 0.14; 2.4 +/- 0.9, respectively). MnSOD did not change in any group. Vitamin E supplementation had no effect on any enzymatic activity and mRNA in both normal and hyperglycemic conditions. Adolescents with early signs of diabetic angiopathy have defective IAP and activity, which are not modified by vitamin E.
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PMID:Effects of vitamin E supplementation on intracellular antioxidant enzyme production in adolescents with type 1 diabetes and early microangiopathy. 1534 73

Large, prospective, clinical trials have confirmed the efficacy of intensive blood-glucose control to prevent the onset and progression of diabetic complications. However, since it is difficult to maintain blood glucose concentrations close to the normal range, the effect of intensive therapy to prevent diabetic complications may be limited. Other approaches are therefore required to prevent the progression of diabetic complications based on the elucidation of the biological mechanisms. In this review, the impacts of mitochondrial reactive oxygen species (ROS) on diabetes-related complications are described. In endothelial cells, high glucose levels increase mitochondrial ROS, and the normalization of mitochondrial ROS production by inhibitors of mitochondrial metabolism, or by the overexpression of UCP-1 or MnSOD, prevents the glucose-induced accumulation of sorbitol, activation of protein kinase C, and formation of advanced glycation end products, all of which are believed to be major molecular mechanisms of diabetic complications. We also demonstrated that 8-hydroxydeoxyguanosine, which represents mitochondrial oxidative damage, was elevated in patients with either retinopathy, albuminuria, or the increased intima-media thickness of carotid arteries compared to patients without diabetic vascular complications. In addition, to investigate the impact of mitochondrial ROS on diabetic retinopathy in vivo, we established a novel transgenic mouse, which specifically expressed MnSOD in endothelial cells. By the introduction of diabetes, levels of urinary 8-hydroxydeoxyguanosine and expressions of VEGF and fibronectin mRNA in retinas were increased in wild type littermates; however, these observations were ameliorated in transgenic mice. Taking the results together, hyperglycemia could induce mitochondrial ROS production, associating it with the pathogenesis of diabetic vascular complications.
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PMID:[Investigation of a novel mechanism of diabetic complications: impacts of mitochondrial reactive oxygen species]. 1880 Jun 28

Retinal mitochondria become dysfunctional and their DNA (mtDNA) is damaged in diabetes. The biogenesis of mitochondrial DNA is tightly controlled by nuclear-mitochondrial transcriptional factors, and translocation of transcription factor A (TFAM) to the mitochondria is essential for transcription and replication. Our aim is to investigate the effects of diabetes on nuclear-mitochondrial communication in the retina and its role in the development of retinopathy. Damage of mtDNA, copy number, and biogenesis (PGC1, NRF1, TFAM) were analyzed in the retinas from streptozotocin-diabetic wild-type (WT) and MnSOD transgenic (Tg) mice. Binding between TFAM and chaperone Hsp70 was quantified by coimmunoprecipitation. The key parameters were confirmed in isolated retinal endothelial cells and in the retinas from human donors with diabetic retinopathy. Diabetes in WT mice increased retinal mtDNA damage and decreased copy number. The gene transcripts of PGC1, NRF1, and TFAM were increased, but mitochondrial accumulation of TFAM was significantly decreased, and the binding of Hsp70 and TFAM was subnormal compared to WT nondiabetic mice. However, Tg diabetic mice were protected from retinal mtDNA damage and alterations in mitochondrial biogenesis. In retinal endothelial cells, high glucose decreased the number of mitochondria, as demonstrated by MitoTracker green staining and by electron microscopy, and impaired the transcriptional factors. Similar alterations in biogenesis were observed in the donors with diabetic retinopathy. Thus, retinal mitochondrial biogenesis is under the control of superoxide radicals and is impaired in diabetes, possibly by decreased transport of TFAM to the mitochondria. Modulation of biogenesis by pharmaceutical or molecular means may provide a potential strategy to retard the development/progression of diabetic retinopathy.
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PMID:Mitochondrial biogenesis and the development of diabetic retinopathy. 2191 Oct 54