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Jesús Silvestre Albert, Gustavo Sánchez-Chávez, Rocio Salceda; Expression levels of Nrf2 at early streptozotocin-induced diabetes in the rat retina. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3568.
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Diabetes mellitus is a metabolic disease that leads to several complications, including retinopathy. There is evidence that hyperglycemia produces oxidative stress in the retina at long-standing diabetes. The cellular redox potential is mainly maintained by the Nuclear transcription factor-erythroid 2 (Nrf2), which control the antioxidant response. Then, we hypothesized that hyperglycemic conditions lead to changes in Nrf2 regulation that in turn trigger oxidative stress.
Adult Long Evans rats were used; diabetes was induced by a single intraperitoneal injection of streptozotocin. Control rats were injected with vehicle. Rats were considered diabetic if blood glucose levels were ≥ 250 mg/dl. Normal and diabetic rats were sacrificed after 7, 20, 30, and 45 days. The expression of Nrf2 and Keap-1 was analyzed in retinal homogenates and in the cytoplasmic and nuclear fractions by Western Blot.
After 20 days of diabetes, we found a slight decrease of Nrf2 expression levels, but a significant increase (30%) was found at 45 days-diabetes. Remarkable, Nrf2 levels in the nuclear fraction were similar in normal and 45 days diabetic rat retina, suggesting decrease of its degradation or increase in its synthesis. Ubiquitinated-Nrf2 was analyzed by immunoprecipitation. Total levels of ubiquitinated Nrf2 were diminished by 40% at 20 and 45 days-diabetes; but levels of ubiquitinated Nrf2 linked to Keap-1 did not change.
These results do not support the existence of oxidative stress at early diabetes induction. Besides, the increase in the cytoplasmic levels of Nrf2 which are not associated to Keap-1 in the retina at early stages of diabetes, suggest a dysregulation of Nrf2 expression, which might lead to future alterations in its redox regulatory activity.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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