title: Proteomic Insight Reveals Elevated Levels of Albumin in Circulating Immune Complexes in Diabetic Plasma.
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.
authors.affiliation: From the ‡Proteomics Facility, Division of Biochemical Sciences, CSIR-National Chemical Laboratory, Pune-411008, India, and Academy of Scientific and Innovative Research (AcSIR), New Delhi, India;
authors.forename: Shweta
authors.initials: S
authors.lastname: Bhat
authors.affiliation: From the ‡Proteomics Facility, Division of Biochemical Sciences, CSIR-National Chemical Laboratory, Pune-411008, India, and Academy of Scientific and Innovative Research (AcSIR), New Delhi, India;
authors.forename: Mashanipalya G
authors.initials: MG
authors.lastname: Jagadeeshaprasad
authors.affiliation: From the ‡Proteomics Facility, Division of Biochemical Sciences, CSIR-National Chemical Laboratory, Pune-411008, India, and Academy of Scientific and Innovative Research (AcSIR), New Delhi, India;
authors.forename: Yugendra R
authors.initials: YR
authors.lastname: Patil
authors.affiliation: §National Center for Cell Science, Pune-411007, India;
authors.forename: Mahemud L
authors.initials: ML
authors.lastname: Shaikh
authors.affiliation: ¶Madras Diabetes Research Foundation, Chennai-600 086, India.
authors.forename: Bhaskaran S
authors.initials: BS
authors.lastname: Regin
authors.affiliation: ¶Madras Diabetes Research Foundation, Chennai-600 086, India.
authors.forename: Viswanathan
authors.initials: V
authors.lastname: Mohan
authors.affiliation: From the ‡Proteomics Facility, Division of Biochemical Sciences, CSIR-National Chemical Laboratory, Pune-411008, India, and Academy of Scientific and Innovative Research (AcSIR), New Delhi, India;
authors.forename: Ashok P
authors.initials: AP
authors.lastname: Giri
authors.affiliation: ¶Madras Diabetes Research Foundation, Chennai-600 086, India.
authors.forename: Muthuswamy
authors.initials: M
authors.lastname: Balasubramanyam
authors.affiliation: §National Center for Cell Science, Pune-411007, India;
authors.forename: Ramanamurthy
authors.initials: R
authors.lastname: Boppana
authors.affiliation: From the ‡Proteomics Facility, Division of Biochemical Sciences, CSIR-National Chemical Laboratory, Pune-411008, India, and Academy of Scientific and Innovative Research (AcSIR), New Delhi, India; mj.kulkarni@ncl.res.in.
authors.forename: Mahesh J
authors.initials: MJ
authors.lastname: Kulkarni
mesh_terms: D000818:Animals; D001798:Blood Proteins / Q000032:analysis* / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D017127:Glycation End Products, Advanced / Q000276:immunology*; D006146:Guanidines / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D040901:Proteomics / Q000379:methods*; D012709:Serum Albumin / Q000032:analysis; D013311:Streptozocin
chemical_list: D001798:Blood Proteins; D016207:Cytokines; D017127:Glycation End Products, Advanced; D006146:Guanidines; D012709:Serum Albumin; D013311:Streptozocin; C004479:pimagedine