02643nas a2200301 4500008004100000022001400041245005500055210005500110260006700165300001200232490000700244520171800251653001701969653001201986653001401998653001102012653002002023653000902043100002502052700002302077700002102100700002402121700002102145700003602166700002802202700002502230856008602255 2015 eng d a1615-985300aInvestigation of phosphoproteome in RAGE signaling0 aInvestigation of phosphoproteome in RAGE signaling a111 RIVER ST, HOBOKEN 07030-5774, NJ USAbWILEY-BLACKWELLcJAN a245-2590 v153 a

The receptor for advanced glycation end products (RAGE) is one of the most important proteins implicated in diabetes, cardiovascular diseases, neurodegenerative diseases, and cancer. It is a pattern recognition receptor by virtue of its ability to interact with multiple ligands, RAGE activates several signal transduction pathways through involvement of various kinases that phosphorylate their respective substrates. Only few substrates have been known to be phosphorylated in response to activation by RAGE (e.g., nuclear factor kappa B); however, it is possible that these kinases can phosphorylate multiple substrates depending upon their expression and localization, leading to altered cellular responses in different cell types and conditions. One such example is, glycogen synthase kinase 3 beta which is known to phosphorylate glycogen synthase, acts downstream to RAGE, and hyperphosphorylates microtubule-associated protein tau causing neuronal damage. Thus, it is important to understand the role of various RAGE-activated kinases and their substrates. Therefore, we have reviewed here the details of RAGE-activated kinases in response to different ligands and their respective phosphoproteome. Furthermore, we discuss the analysis of the data mined for known substrates of these kinases from the PhosphoSitePlus (http://www.phosphosite.org) database, and the role of some of the important substrates involved in cancer, diabetes, cardiovascular diseases, and neurodegenerative diseases. In summary, this review provides information on RAGE-activated kinases and their phosphoproteome, which will be helpful in understanding the possible role of RAGE and its ligands in progression of diseases.

10aCell biology10aDisease10aGlycation10aKinase10aPhosphoproteome10aRAGE1 aBatkulwar, Kedar, B.1 aBansode, Sneha, B.1 aPatil, Gouri, V.1 aGodbole, Rashmi, K.1 aKazi, Rubina, S.1 aChinnathambi, Subashchandrabose1 aShanmugam, Dhanasekaran1 aKulkarni, Mahesh, J. uhttps://library.ncl.res.in/content/investigation-phosphoproteome-rage-signaling-002873nas a2200325 4500008004100000022001400041245012300055210006900178260006700247300001200314490000700326520171600333653003602049653001002085653002702095653001102122653001402133653001302147653001502160100002502175700002102200700002102221700002702242700003902269700002302308700003602331700002502367700002402392856013102416 2015 eng d a1474-971800aRifampicin reduces advanced glycation end products and activates DAF-16 to increase lifespan in Caenorhabditis elegans0 aRifampicin reduces advanced glycation end products and activates a111 RIVER ST, HOBOKEN 07030-5774, NJ USAbWILEY-BLACKWELLcJUN a463-4730 v143 a

Advanced glycation end products (AGEs) are formed when glucose reacts nonenzymatically with proteins; these modifications are implicated in aging and pathogenesis of many age-related diseases including type II diabetes, atherosclerosis, and neurodegenerative disorders. Thus, pharmaceutical interventions that can reduce AGEs may delay age-onset diseases and extend lifespan. Using LC-MSE, we show that rifampicin (RIF) reduces glycation of important cellular proteins in vivo and consequently increases lifespan in Caenorhabditis elegans by up to 60%. RIF analog rifamycin SV (RSV) possesses similar properties, while rifaximin (RMN) lacks antiglycation activity and therefore fails to affect lifespan positively. The efficacy of RIF and RSV as potent antiglycating agents may be attributed to the presence of a p-dihydroxyl moiety that can potentially undergo spontaneous oxidation to yield highly reactive p-quinone structures, a feature absent in RMN. We also show that supplementing rifampicin late in adulthood is sufficient to increase lifespan. For its effect on longevity, rifampicin requires DAF-18 (nematode PTEN) as well as JNK-1 and activates DAF-16, the FOXO homolog. Interestingly, the drug treatment modulates transcription of a different subset of DAF-16 target genes, those not controlled by the conserved Insulin-IGF-1-like signaling pathway. RIF failed to increase the lifespan of daf-16 null mutant despite reducing glycation, showing thereby that DAF-16 may not directly affect AGE formation. Together, our data suggest that the dual ability to reduce glycation in vivo and activate prolongevity processes through DAF-16 makes RIF and RSV effective lifespan-extending interventions.

10aadvanced glycation end products10aaging10aCaenorhabditis elegans10aDAF-1610aGlycation10alifespan10arifampicin1 aGolegaonkar, Sandeep1 aTabrez, Syed, S.1 aPandit, Awadhesh1 aSethurathinam, Shalini1 aJagadeeshaprasad, Mashanipalya, G.1 aBansode, Sneha, B.1 aSampathkumar, Srinivasa-Gopalan1 aKulkarni, Mahesh, J.1 aMukhopadhyay, Arnab uhttps://library.ncl.res.in/content/rifampicin-reduces-advanced-glycation-end-products-and-activates-daf-16-increase-lifespan-002342nas a2200265 4500008004100000022001400041245016300055210006900218260012700287300001200414490000700426520130200433653001301735653001301748653001701761653001401778653001101792653001901803100002601822700002501848700002301873700002501896700002501921856013001946 2016 eng d a1138-754800aDietary flaxseed oil and fish oil ameliorates renal oxidative stress, protein glycation, and inflammation in streptozotocin-nicotinamide-induced diabetic rats0 aDietary flaxseed oil and fish oil ameliorates renal oxidative st aCAMPUS UNIV, CARRETERA DEL SADAR S-N, APARTADO 177, 31080 PAMPLONA, SPAINbSERVICIO PUBLICACIONES UNIVERSIDAD NAVARRAcJUN a327-3360 v723 a

Protective and prophylactic effects of omega-3 fatty acids on oxidative stress and inflammation are well known. We assessed beneficial effects of flaxseed oil and fish oil on streptozotocin (65 mg/kg; i.p.)-nicotinamide (110 mg/kg; i.p.) induced diabetic rats by studying renal expression of antioxidant and inflammatory genes. Diabetic rats given 10 % flaxseed oil or 10 % fish oil diet for 35 days showed significant decrease in renal lipid peroxidation. Flaxseed oil diet resulted in up-regulation of renal superoxide dismutase-1 (SOD-1) (activity and expression) and glutathione peroxidase-1 (GPx-1) expression. Furthermore, both diets up-regulated catalase (CAT) (activity and expression) and down-regulated heme oxygenase-1 (HO-1) expression. Both diets were able to limit the renal advanced glycation end products (AGEs) formation and reduced receptor of AGE (RAGE) protein expression significantly. Expressions of interleukin-6 (IL-6) and NF-kappa B p65 subunit were down-regulated significantly by flaxseed oil or fish oil diet. The histological tubular injuries were also lowered by both diets. These results suggest that dietary omega-3 fatty acids may slow the progression of diabetic nephropathy (DN) associated with oxidative stress, glycation, and inflammation in the kidney.

10aDiabetes10aFish oil10aFlaxseed oil10aGlycation10aKidney10aStreptozotocin1 aJangale, Nivedita, M.1 aDevarshi, Prasad, P.1 aBansode, Sneha, B.1 aKulkarni, Mahesh, J.1 aHarsulkar, Abhay, M. uhttps://library.ncl.res.in/content/dietary-flaxseed-oil-and-fish-oil-ameliorates-renal-oxidative-stress-protein-glycation-and02638nas a2200277 4500008004100000022001400041245011500055210006900170260000900239300001100248490000900259520174400268653000802012653001302020653001402033653001802047653001202065653000902077100002202086700002302108700002102131700003202152700002202184700002502206856012902231 2021 eng d a0925-443900aMolecular investigation of glycated insulin-induced insulin resistance via insulin signaling and AGE-RAGE axis0 aMolecular investigation of glycated insulininduced insulin resis cFEB  a1660290 v18673 a

Hyperglycemic condition in diabetes promotes glycation of various plasma proteins including insulin. Glycation of insulin has been reported to reduce its biological activity. Reduced biological activity of glycated insulin could be either due to reduced affinity for the insulin receptor and impaired insulin signaling, or it can act as a ligand for the receptor for advanced glycation end products (RAGE) and activates oxidative stress and pro-inflammatory pathways leading to insulin resistance. This study investigates the effect of glycated insulin on both insulin and RAGE signaling. Glycated insulin treatment to Chinese hamster ovary (CHO-IR-GLUT4) cells stably expressing insulin receptor (IR) and glucose transporter fused with a green fluorescent protein (GLUT4-GFP) resulted in the impairment of insulin signaling, as the phosphorylation of IR and AKT significantly reduced, which affected GLUT4 translocation and glucose uptake. Moreover, it also activated RAGE signaling as observed by increased expression of NADPH oxidase accompanied by an increase in reactive oxygen species (ROS). Immunofluorescence study indicated the translocation of NF-kappa B to the nucleus upon treatment of glycated insulin. This was associated with increased RAGE expression, Caspase 3, and cell death. Downregulation of RAGE with the losartan treatment restored the impaired insulin signaling and glucose uptake. Additionally, in silico study demonstrated that glycated insulin has reduced binding affinity to insulin receptor and increased binding affinity to RAGE. Overall, this study demonstrates the role of glycated insulin in exacerbating insulin resistance by impairing insulin signaling as well as stimulating AGE-RAGE signaling.

10aAGE10aDiabetes10aGlycation10aHyperglycemia10ainsulin10aRAGE1 aWalke, Prachi, B.1 aBansode, Sneha, B.1 aMore, Nikita, P.1 aChaurasiya, Arvindkumar, H.1 aJoshi, Rakesh, S.1 aKulkarni, Mahesh, J. uhttps://library.ncl.res.in/content/molecular-investigation-glycated-insulin-induced-insulin-resistance-insulin-signaling-and