Abstract
We previously proposed that hyperglycemia-induced mitochondrial reactive oxygen species (mtROS) generation is a key event in the development of diabetic complications. Interestingly, some common aspects exist between hyperglycemia and hypoxia-induced phenomena. Thus, hyperglycemia may induce cellular hypoxia, and this phenomenon may also be involved in the pathogenesis of diabetic complications. In endothelial cells (ECs), cellular hypoxia increased after incubation with high glucose (HG). A similar phenomenon was observed in glomeruli of diabetic mice. HG-induced cellular hypoxia was suppressed by mitochondria blockades or manganese superoxide dismutase (MnSOD) overexpression, which is a specific SOD for mtROS. Overexpression of MnSOD also increased the expression of aquaporin-1 (AQP1), a water and oxygen channel. AQP1 overexpression in ECs suppressed hyperglycemia-induced cellular hypoxia, endothelin-1 and fibronectin overproduction, and apoptosis. Therefore, hyperglycemia-induced cellular hypoxia and mtROS generation may promote hyperglycemic damage in a coordinated manner.
Highlights
Diabetes causes complications including retinopathy, nephropathy, neuropathy, and macroangiopathy
We previously demonstrated that mitochondrial reactive oxygen species generation is the major cause of diabetes-induced oxidative stress, and that it causes other metabolic abnormalities, such as polyol pathway activation, advanced glycation end products formation, and protein kinase C activation [1]
To evaluate the association of mitochondrial reactive oxygen species (mtROS) generation with hyperglycemia-induced cellular hypoxia, we investigated the effect of manganese superoxide dismutase (MnSOD) overexpression on cellular hypoxia
Summary
Diabetes causes complications including retinopathy, nephropathy, neuropathy, and macroangiopathy. To minimize the risk of diabetic complications, blood glucose, blood pressure, and lipids should be properly controlled. We have various means of treating diabetes, there are still many patients who develop diabetic complications. Other approaches based on the elucidation of mechanisms of diabetic complications may be required to prevent diabetic complications. We previously demonstrated that mitochondrial reactive oxygen species (mtROS) generation is the major cause of diabetes-induced oxidative stress, and that it causes other metabolic abnormalities, such as polyol pathway activation, advanced glycation end products formation, and protein kinase C activation [1].
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