Diwesh Chawla1, Savita Bansal2, Basu Dev Banerjee3, Sri Venkata Madhu4, Om Prakash Kalra5, Ashok Kumar Tripathi6. 1. Biochemistry and Immunology Laboratory, Department of Biochemistry, University College of Medical Sciences (University of Delhi) and G.T.B. Hospital, Dilshad Garden, Delhi 110095, India. Electronic address: diweshchawla@yahoo.co.in. 2. Biochemistry and Immunology Laboratory, Department of Biochemistry, University College of Medical Sciences (University of Delhi) and G.T.B. Hospital, Dilshad Garden, Delhi 110095, India. Electronic address: bansalsavita_1916@yahoo.com. 3. Biochemistry and Immunology Laboratory, Department of Biochemistry, University College of Medical Sciences (University of Delhi) and G.T.B. Hospital, Dilshad Garden, Delhi 110095, India. Electronic address: banerjeebd@hotmail.com. 4. Department of Medicine, University College of Medical Sciences (University of Delhi) and G.T.B. Hospital, Dilshad Garden, Delhi 110095, India. Electronic address: drsvmadhu@gmail.com. 5. Department of Medicine, University College of Medical Sciences (University of Delhi) and G.T.B. Hospital, Dilshad Garden, Delhi 110095, India. Electronic address: opkalra1@yahoo.com. 6. Biochemistry and Immunology Laboratory, Department of Biochemistry, University College of Medical Sciences (University of Delhi) and G.T.B. Hospital, Dilshad Garden, Delhi 110095, India. Electronic address: aktripathiucms@gmail.com.
Abstract
AIMS: Vascular complications are the major causes of morbidity and mortality in diabetic subjects. Interaction of advanced glycation end products (AGEs) with their receptor (RAGE) induces signal transduction that culminates in vascular complications. Therefore, in the present study we investigated the dependence of RAGE expression on circulating AGEs and evaluated the outcome of AGE-RAGE interaction by the oxidative stress and nature of vascular complications in type 2 diabetes mellitus (T2DM) patients. METHODS: RAGE expression was determined by quantitative real-time PCR and western blotting, serum AGEs were estimated by ELISA and spectrofluorometry and oxidative stress markers namely protein carbonyl (PCO), advanced oxidation protein products (AOPP) and lipid peroxidation (MDA) were assayed spectrophotometerically in 75 T2DM patients (DM without vascular complication n=25; DM with microvascular complications n=25; DM with macrovascular complications n=25) and 25 healthy controls. RESULTS: Serum AGE level was significantly higher in diabetic patients having vascular complications as compared to T2DM without complications (p<0.01). RAGE m-RNA expression level in PBMCs assayed by quantitative real time PCR was four times higher in diabetic subjects without vascular complications while DM patients having microvascular and macrovascular complications showed 12 fold and 8 fold higher RAGE m-RNA expression respectively compared to healthy controls. Circulating AGE level showed significant positive correlation with RAGE m-RNA expression and oxidative stress markers. CONCLUSION: AGE-mediated exacerbation of RAGE expression may contribute to oxidative stress generation that plays a key role in pathogenesis of vascular complications in diabetes.
AIMS: Vascular complications are the major causes of morbidity and mortality in diabetic subjects. Interaction of advanced glycation end products (AGEs) with their receptor (RAGE) induces signal transduction that culminates in vascular complications. Therefore, in the present study we investigated the dependence of RAGE expression on circulating AGEs and evaluated the outcome of AGE-RAGE interaction by the oxidative stress and nature of vascular complications in type 2 diabetes mellitus (T2DM) patients. METHODS:RAGE expression was determined by quantitative real-time PCR and western blotting, serum AGEs were estimated by ELISA and spectrofluorometry and oxidative stress markers namely protein carbonyl (PCO), advanced oxidation protein products (AOPP) and lipid peroxidation (MDA) were assayed spectrophotometerically in 75 T2DM patients (DM without vascular complication n=25; DM with microvascular complications n=25; DM with macrovascular complications n=25) and 25 healthy controls. RESULTS: Serum AGE level was significantly higher in diabeticpatients having vascular complications as compared to T2DM without complications (p<0.01). RAGE m-RNA expression level in PBMCs assayed by quantitative real time PCR was four times higher in diabetic subjects without vascular complications while DMpatients having microvascular and macrovascular complications showed 12 fold and 8 fold higher RAGE m-RNA expression respectively compared to healthy controls. Circulating AGE level showed significant positive correlation with RAGE m-RNA expression and oxidative stress markers. CONCLUSION: AGE-mediated exacerbation of RAGE expression may contribute to oxidative stress generation that plays a key role in pathogenesis of vascular complications in diabetes.
Authors: Andréa E M Stinghen; Ziad A Massy; Helen Vlassara; Gary E Striker; Agnès Boullier Journal: J Am Soc Nephrol Date: 2015-08-26 Impact factor: 10.121
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