@article { ISI:000298860100004, title = {Proteomic analysis of glycated proteins from streptozotocin-induced diabetic rat kidney}, journal = {Molecular Biotechnology}, volume = {50}, number = {1}, year = {2012}, month = {JAN}, pages = {28-38}, publisher = {HUMANA PRESS INC}, address = {999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA}, abstract = {

Glycation of proteins leading to formation of advanced glycation end products (AGEs) has been considered as one of the important causes of diabetic nephropathy. Therefore, in this study, glycated proteins were detected by anti-AGE antibodies from kidney of streptozotocin-induced diabetic rat showing nephropathic symptoms, by using two dimensional electrophoresis and western blot analysis. These glycated proteins were identified and characterized by using combination of peptide mass finger printing and tandem mass spectrometric approaches. Glycated proteins identified included proteins from metabolic pathways, oxidative stress, cell signaling, and transport. Several of the proteins modified by glycation were involved in glucose metabolism. The extent of glycation was higher in diabetes compared to control, in the glycated proteins that were common to both control and diabetic kidney. Two dimensional electrophoresis proteins profiling of glycated proteins suggest that four of the glycated proteins were significantly up regulated in diabetes.

}, keywords = {AGE, Diabetes, Glucose toxicity, Nephropathy, Post-translation modification}, issn = {1073-6085}, doi = {10.1007/s12033-011-9409-3}, author = {Chougale, Ashok D. and Bhat, Shweta P. and Bhujbal, Swapnil V. and Zambare, Mandar R. and Puntambekar, Shraddha and Somani, Rahul S. and Boppana, Ramanamurthy and Giri, Ashok P. and Kulkarni, Mahesh J.} } @article { ISI:000325608800002, title = {Proteome wide reduction in AGE modification in streptozotocin induced diabetic mice by hydralazine mediated transglycation}, journal = {Scientific Reports}, volume = {3}, year = {2013}, month = {OCT}, pages = {2941}, publisher = {NATURE PUBLISHING GROUP}, address = {MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND}, abstract = {

The non-enzymatic reaction between glucose and protein can be chemically reversed by transglycation. Here we report the transglycation activity of hydralazine using a newly developed MALDI-TOF-MS based assay. Hydralazine mediated transglycation of HbA1c, plasma proteins and kidney proteins was demonstrated in streptozotocin (STZ) induced diabetic mice, as evidenced by decrease in protein glycation, as well as presence of hydralazine-glucose conjugate in urine of diabetic mice treated with hydralazine. Hydralazine down regulated the expression of Receptor for Advanced Glycation End products (RAGE), NADPH oxidase (NOX), and super oxide dismutase (SOD). These findings will provide a new dimension for developing intervention strategies for the treatment of glycation associated diseases such as diabetes complications, atherosclerosis, and aging.

}, issn = {2045-2322}, doi = {10.1038/srep02941}, author = {Kesavan, Suresh K. and Bhat, Shweta and Golegaonkar, Sandeep B. and Jagadeeshaprasad, Mashanipalya G. and Deshmukh, Arati B. and Patil, Harshal S. and Bhosale, Santosh D. and Shaikh, Mahemud L. and Thulasiram, Hirekodathakallu V. and Boppana, Ramanamurthy and Kulkarni, Mahesh J.} } @article { ISI:000368189500001, title = {Potential dual role of eugenol in inhibiting advanced glycation end products in diabetes: proteomic and mechanistic insights}, journal = {Scientific Reports}, volume = {6}, year = {2016}, month = {JAN}, publisher = {NATURE PUBLISHING GROUP}, address = {MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND}, abstract = {

Medicinally important genus Ocimum harbors a vast pool of chemically diverse metabolites. Current study aims at identifying anti-diabetic candidate compounds from Ocimum species. Major metabolites in O. kilimandscharicum, O. tenuiflorum, O. gratissimum were purified, characterized and evaluated for anti-glycation activity. In vitro inhibition of advanced glycation end products (AGEs) by eugenol was found to be highest. Preliminary biophysical analysis and blind docking studies to understand eugenol-albumin interaction indicated eugenol to possess strong binding affinity for surface exposed lysines. However, binding of eugenol to bovine serum albumin (BSA) did not result in significant change in secondary structure of protein. In vivo diabetic mice model studies with eugenol showed reduction in blood glucose levels by 38\% likely due to inhibition of alpha-glucosidase while insulin and glycated hemoglobin levels remain unchanged. Western blotting using anti-AGE antibody and mass spectrometry detected notably fewer AGE modified peptides upon eugenol treatment both in vivo and in vitro. Histopathological examination revealed comparatively lesser lesions in eugenol-treated mice. Thus, we propose eugenol has dual mode of action in combating diabetes; it lowers blood glucose by inhibiting a-glucosidase and prevents AGE formation by binding to epsilon-amine group on lysine, protecting it from glycation, offering potential use in diabetic management.

}, issn = {2045-2322}, doi = {10.1038/srep18798}, author = {Singh, Priyanka and Jayaramaiah, Ramesha H. and Agawane, Sachin B. and Vannuruswamy, Garikapati and Korwar, Arvind M. and Anand, Atul and Dhaygude, Vitthal S. and Shaikh, Mahemud L. and Joshi, Rakesh S. and Boppana, Ramanamurthy and Kulkarni, Mahesh J. and Thulasiram, Hirekodathakallu V. and Giri, Ashok P.} } @article { ISI:000377822900018, title = {Proteomic insight reveals elevated levels of albumin in circulating immunecomplexes in diabetic plasma}, journal = {Molecular \& Cellular Proteomics}, volume = {15}, number = {6}, year = {2016}, month = {JUN}, pages = {2011-2020}, publisher = {AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC}, address = {9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA}, abstract = {

A Hyperglycemic condition in diabetes promotes formation of advanced glycation end products, which are known to elicit immune response and form complexes with immunoglobulins called circulating immune complexes. To investigate the involvement of advanced glycation end product (AGE)-modified proteins in the elicitation of an immune response, circulating immune complexes were isolated and proteins associated were identified and characterized. Label-free-based mass spectrometric analysis of circulating immune complexes in clinical plasma of prediabetic, newly diagnosed diabetes, and diabetic microalbuminurea revealed elevated levels of serum albumin in the circulating immune complexes, which were also observed to be AGE modified. Further, to examine the role of glycation, circulating immune complexeswere analyzed in the streptozotocin-induced diabetic mice treated with or without aminoguanidine, a prototype glycation inhibitor. Mass spectrometric analysis of circulating immune complexes showed elevated levels of serum albumin in plasma from diabetic mice over that of control animals. Aminoguanidine-treated diabetic mice displayed decreased AGE modification of plasma albumin, accompanied by a reduced level of albumin in the circulating immune complexes. In addition, elevated levels of proinflammatory cytokines such as IL-1b, IL-2, and TNF-alpha were observed in diabetes, which were reduced with aminoguanidine treatment, suggesting the involvement of glycation in the immune response.

}, issn = {1535-9476}, doi = {10.1074/mcp.M116.058008}, author = {Bhat, Shweta and Jagadeeshaprasad, Mashanipalya G. and Patil, Yugendra R. and Shaikh, Mahemud L. and Regin, Bhaskaran S. and Mohan, Viswanathan and Giri, Ashok P. and Balasubramanyam, Muthuswamy and Boppana, Ramanamurthy and Kulkarni, Mahesh J.} }