01910nas a2200265 4500008004100000022001400041245012700055210006900182260009000251300000900341490000600350520086400356100002401220700001701244700002901261700003901290700002401329700002301353700002501376700002401401700003701425700002601462700002501488856013101513 2013 eng d a2045-232200aProteome wide reduction in AGE modification in streptozotocin induced diabetic mice by hydralazine mediated transglycation0 aProteome wide reduction in AGE modification in streptozotocin in aMACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLANDbNATURE PUBLISHING GROUPcOCT a29410 v33 a

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.

1 aKesavan, Suresh, K.1 aBhat, Shweta1 aGolegaonkar, Sandeep, B.1 aJagadeeshaprasad, Mashanipalya, G.1 aDeshmukh, Arati, B.1 aPatil, Harshal, S.1 aBhosale, Santosh, D.1 aShaikh, Mahemud, L.1 aThulasiram, Hirekodathakallu, V.1 aBoppana, Ramanamurthy1 aKulkarni, Mahesh, J. uhttps://library.ncl.res.in/content/proteome-wide-reduction-age-modification-streptozotocin-induced-diabetic-mice-hydralazine-002556nas a2200277 4500008004100000022001400041245012900055210006900184260009000253490000600343520147700349100002001826700002901846700002401875700002901899700002301928700001601951700002601967700002401993700002202017700002602039700002502065700003702090700002002127856013102147 2016 eng d a2045-232200aPotential dual role of eugenol in inhibiting advanced glycation end products in diabetes: proteomic and mechanistic insights0 aPotential dual role of eugenol in inhibiting advanced glycation  aMACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLANDbNATURE PUBLISHING GROUPcJAN0 v63 a

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.

1 aSingh, Priyanka1 aJayaramaiah, Ramesha, H.1 aAgawane, Sachin, B.1 aVannuruswamy, Garikapati1 aKorwar, Arvind, M.1 aAnand, Atul1 aDhaygude, Vitthal, S.1 aShaikh, Mahemud, L.1 aJoshi, Rakesh, S.1 aBoppana, Ramanamurthy1 aKulkarni, Mahesh, J.1 aThulasiram, Hirekodathakallu, V.1 aGiri, Ashok, P. uhttps://library.ncl.res.in/content/potential-dual-role-eugenol-inhibiting-advanced-glycation-end-products-diabetes-proteomic-002505nas a2200253 4500008004100000022001400041245010700055210006900162260010300231300001400334490000700348520151500355100001701870700003901887700002401926700002401950700002501974700002301999700002002022700003202042700002602074700002502100856012602125 2016 eng d a1535-947600aProteomic insight reveals elevated levels of albumin in circulating immunecomplexes in diabetic plasma0 aProteomic insight reveals elevated levels of albumin in circulat a9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USAbAMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INCcJUN a2011-20200 v153 a

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.

1 aBhat, Shweta1 aJagadeeshaprasad, Mashanipalya, G.1 aPatil, Yugendra, R.1 aShaikh, Mahemud, L.1 aRegin, Bhaskaran, S.1 aMohan, Viswanathan1 aGiri, Ashok, P.1 aBalasubramanyam, Muthuswamy1 aBoppana, Ramanamurthy1 aKulkarni, Mahesh, J. uhttps://library.ncl.res.in/content/proteomic-insight-reveals-elevated-levels-albumin-circulating-immunecomplexes-diabetic