title: Identification of C1q as a Binding Protein for Advanced Glycation End Products.
abstract: Advanced glycation end products (AGEs) make up a heterogeneous group of molecules formed from the nonenzymatic reaction of reducing sugars with the free amino groups of proteins. The abundance of AGEs in a variety of age-related diseases, including diabetic complications and atherosclerosis, and their pathophysiological effects suggest the existence of innate defense mechanisms. Here we examined the presence of serum proteins that are capable of binding glycated bovine serum albumin (AGEs-BSA), prepared upon incubation of BSA with dehydroascorbate, and identified complement component C1q subcomponent subunit A as a novel AGE-binding protein in human serum. A molecular interaction analysis showed the specific binding of C1q to the AGEs-BSA. In addition, we identified DNA-binding regions of C1q, including a collagen-like domain, as the AGE-binding site and established that the amount of positive charge on the binding site was the determining factor. C1q indeed recognized several other modified proteins, including acylated proteins, suggesting that the binding specificity of C1q might be ascribed, at least in part, to the electronegative potential of the ligand proteins. We also observed that C1q was involved in the AGEs-BSA-activated deposition of complement proteins, C3b and C4b. In addition, the AGEs-BSA mediated the proteolytic cleavage of complement protein 5 to release C5a. These findings provide the first evidence of AGEs as a new ligand recognized by C1q, stimulating the C1q-dependent classical complement pathway.
authors.affiliation: Graduate School of Bioagricultural Sciences, Nagoya University , Nagoya 464-8601, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Chikazawa
authors.affiliation: Graduate School of Bioagricultural Sciences, Nagoya University , Nagoya 464-8601, Japan.|PRESTO, Japan Science and Technology Agency (JST) , Kawaguchi, Saitama 332-0012, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Shibata
authors.affiliation: Graduate School of Bioagricultural Sciences, Nagoya University , Nagoya 464-8601, Japan.
authors.forename: Yukinori
authors.initials: Y
authors.lastname: Hatasa
authors.affiliation: Graduate School of Bioagricultural Sciences, Nagoya University , Nagoya 464-8601, Japan.
authors.forename: Sayumi
authors.initials: S
authors.lastname: Hirose
authors.affiliation: Graduate School of Bioagricultural Sciences, Nagoya University , Nagoya 464-8601, Japan.
authors.forename: Natsuki
authors.initials: N
authors.lastname: Otaki
authors.affiliation: Graduate School of Bioagricultural Sciences, Nagoya University , Nagoya 464-8601, Japan.
authors.forename: Fumie
authors.initials: F
authors.lastname: Nakashima
authors.affiliation: Graduate School of Bioagricultural Sciences, Nagoya University , Nagoya 464-8601, Japan.
authors.forename: Mika
authors.initials: M
authors.lastname: Ito
authors.affiliation: National Food Research Institute , 2-1-12 Kannondai, Tsukuba, Ibaraki 305-8642, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Machida
authors.affiliation: Department of Nephrology, Graduate School of Medical Sciences, Nagoya University , Nagoya 464-8601, Japan.
authors.forename: Shoichi
authors.initials: S
authors.lastname: Maruyama
authors.affiliation: Graduate School of Bioagricultural Sciences, Nagoya University , Nagoya 464-8601, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Uchida
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002417:Cattle; D015922:Complement C1q / Q000378:metabolism*; D003179:Complement C3b / Q000378:metabolism; D015935:Complement C4b / Q000378:metabolism; D015936:Complement C5a / Q000378:metabolism; D003171:Complement Pathway, Classical; D003683:Dehydroascorbic Acid / Q000378:metabolism; D004560:Electricity; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D011485:Protein Binding; D021122:Protein Subunits / Q000378:metabolism; D044967:Serum; D012710:Serum Albumin, Bovine / Q000378:metabolism
chemical_list: D017127:Glycation End Products, Advanced; D021122:Protein Subunits; D012710:Serum Albumin, Bovine; D015922:Complement C1q; D003179:Complement C3b; D015935:Complement C4b; D015936:Complement C5a; D003683:Dehydroascorbic Acid