Abstract
BackgroundForkhead box ‘O’ transcription factors (FoxOs) are implicated in the pathogenesis of type2 diabetes and other metabolic diseases. Abnormal activity of FoxOs was reported in the glucose and insulin metabolism. Expression of FoxO proteins was reported in ocular tissues; however their function under hyperglycemic conditions was not examined.MethodsHuman lens epithelial cell line was used to study the function of FoxO proteins. Immunofluorescence, flow cytometry and Western blotting were employed to detect the FoxO proteins under the conditions of hyperglycemia.ResultsIn this study we examined the role of FoxO3a in hyperglycemia-induced oxidative stress in human lens epithelial cells. FoxO3a protein expression was elevated in a dose- and time-dependent fashion after high glucose treatment. Anti-oxidant defense mechanisms of the lens epithelial cells were diminished as evidenced from loss of mitochondrial membrane integrity and lowered MnSOD after 72 h treatment with high glucose. Taken together, FoxO3a acts as a sensitive indicator of oxidative stress and cell homeostasis in human lens epithelial cells during diabetic conditions.ConclusionFoxO3a is an early stress response protein to glucose toxicity in diabetic conditions.
Highlights
Type 2 Diabetes (T2D) is a metabolic disorder characterized by elevated high blood glucose levels due to relative insulin deficiency or insulin resistance [1]
Cells were treated with different concentrations of glucose ranging from 5.5 to 35 mM for 72 h and we examined the expression of three Forkhead box O (FoxO) proteins – FoxO1, FoxO3a and FoxO4
We investigated the effect of 25 mM high glucose at various time points starting 0–72 h and compared FoxO3a expression with low glucose concentration (5.5 mM)
Summary
Type 2 Diabetes (T2D) is a metabolic disorder characterized by elevated high blood glucose levels due to relative insulin deficiency or insulin resistance [1]. In addition to age and obesity, hyperglycemia-induced oxidative stress is thought to be a major risk factor in the development of various diabetic complications that affect the well-being of eye, heart, kidney, nerves, and blood vessels [2], [3]. Hyperglycemia exerts its effects via several mechanisms including increased polyols pathway flux, increased formation of advanced glycation end products (AGE), activation of protein kinase C (PKC) and elevated levels of mitochondrial ROS in the affected tissues. Abnormal activity of FoxOs was reported in the glucose and insulin metabolism. Expression of FoxO proteins was reported in ocular tissues; their function under hyperglycemic conditions was not examined
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