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Lutein reverses hyperglycemia-mediated blockage of Nrf2 translocation by modulating the activation of intracellular protein kinases in retinal pigment epithelial (ARPE-19) cells.

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Relation http://ir.cftri.com/14669/
https://doi.org/10.1007/s12079-019-00539-1
 
Title Lutein reverses hyperglycemia-mediated blockage
of Nrf2 translocation by modulating the activation of intracellular
protein kinases in retinal pigment epithelial (ARPE-19) cells.
 
Creator Arpitha, H. S.
Ganesan, P.
 
Subject 14 Carotenoid Chemistry
04 Diabetes Mellitus
 
Description Diabetic retinopathy (DR) is a major cause of acquired blindness among working adults. The retinal pigment epithelium (RPE),
constitutes an outer blood-retinal barrier, is vastly affected in diabetic humans and animals. Lower levels of lutein in the serum and
retina of diabetic population, and beneficial effects of carotenoids supplementation in diabetic retinopathy patients created an interest
to examine the protective effect of lutein on hyperglycemia-mediated changes in oxidative stress and antioxidant defense system in
ARPE-19 cells. The WST-1 assay was performed to analyze the impact of glucose, and lutein on the viability of ARPE-19. The
intracellular oxidative stress was measured by a DCF (dichlorofluorescein) assay, mitochondrial membrane potential (MMP) was
monitored using a JC-10 MMP assay kit and GSH level was examined using GSH/GSSG ratio detection kit. The oxidative stress
markers, protein carbonyl and malondialdehyde were spectrophotometrically measured using 2,4-dinitrophenylhydrazine and 2-
thiobarbituric acid, respectively. The expression of endogenous antioxidant enzymes and regulatory proteins in ARPE-19 was
quantified by western blotting. The localization of Nrf2 protein was examined by immunofluorescent staining. The results show that
lutein (up to 1.0 μM) did not affect the viability of ARPE-19 grown in both normal and high-glucose conditions. Lutein treatment
blocked high glucose-mediated elevation of intracellular ROS, protein carbonyl and malondialdehyde content in ARPE-19 cells.
The decreased MMP and GSH levels observed in ARPE-19 grown under high-glucose condition were rescued by lutein treatment.
Further, lutein protected high glucose-mediated down-regulation of a redox-sensitive transcription factor, Nrf2, and antioxidant
enzymes, SOD2, HO-1, and catalase. This protective effect of lutein was linked with activated nuclear translocation of Nrf2, which
was associated with increased activation of regulatory proteins such as Erk and AKT. Our study indicates that improving the
concentration of lutein in the retina could protect RPE from diabetes-associated damage.
 
Date 2020
 
Type Article
PeerReviewed
 
Format pdf
 
Language en
 
Identifier http://ir.cftri.com/14669/1/Journal%20of%20Cell%20Communication%20and%20Signaling%20%282020%29%2014207%E2%80%93221.pdf
Arpitha, H. S. and Ganesan, P. (2020) Lutein reverses hyperglycemia-mediated blockage of Nrf2 translocation by modulating the activation of intracellular protein kinases in retinal pigment epithelial (ARPE-19) cells. Journal of Cell Communication and Signaling, 14. pp. 207-221.