title: A disulfide-bond A oxidoreductase-like protein (DsbA-L) regulates adiponectin multimerization.
abstract: Impairments in adiponectin multimerization lead to defects in adiponectin secretion and function and are associated with diabetes, yet the underlying mechanisms remain largely unknown. We have identified an adiponectin-interacting protein, previously named GST-kappa, by yeast 2-hybrid screening. The adiponectin-interacting protein contains 2 thioredoxin domains and has very little sequence similarity to other GST isoforms. However, this protein shares high sequence and secondary structure homology to bacterial disulfide-bond A oxidoreductase (DsbA) and is thus renamed DsbA-like protein (DsbA-L). DsbA-L is highly expressed in adipose tissue, and its expression level is negatively correlated with obesity in mice and humans. DsbA-L expression in 3T3-L1 adipocytes is stimulated by the insulin sensitizer rosiglitazone and inhibited by the inflammatory cytokine TNFalpha. Overexpression of DsbA-L promoted adiponectin multimerization while suppressing DsbA-L expression by RNAi markedly and selectively reduced adiponectin levels and secretion in 3T3-L1 adipocytes. Our results identify DsbA-L as a key regulator for adiponectin biosynthesis and uncover a potential new target for developing therapeutic drugs for the treatment of insulin resistance and its associated metabolic disorders.
authors.affiliation: Department of Pharmacology, University of Texas Health Science Center, San Antonio, TX 78229, USA.
authors.forename: Meilian
authors.initials: M
authors.lastname: Liu
authors.forename: Lijun
authors.initials: L
authors.lastname: Zhou
authors.forename: Aimin
authors.initials: A
authors.lastname: Xu
authors.forename: Karen S L
authors.initials: KS
authors.lastname: Lam
authors.forename: Michael D
authors.initials: MD
authors.lastname: Wetzel
authors.forename: Ruihua
authors.initials: R
authors.lastname: Xiang
authors.forename: Jingjing
authors.initials: J
authors.lastname: Zhang
authors.forename: Xiaoban
authors.initials: X
authors.lastname: Xin
authors.forename: Lily Q
authors.initials: LQ
authors.lastname: Dong
authors.forename: Feng
authors.initials: F
authors.lastname: Liu
mesh_terms: D041721:3T3-L1 Cells; D052242:Adiponectin / Q000737:chemistry* / Q000378:metabolism; D000328:Adult; D000818:Animals; D055162:Biocatalysis; D001704:Biopolymers / Q000737:chemistry*; D016022:Case-Control Studies; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005982:Glutathione Transferase / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D018832:Molecular Chaperones / Q000378:metabolism / Q000502:physiology*; D009765:Obesity / Q000378:metabolism; D017510:Protein Folding; D011499:Protein Processing, Post-Translational; D034622:RNA Interference; D014158:Transcription, Genetic; D020798:Two-Hybrid System Techniques
chemical_list: D052242:Adiponectin; D001704:Biopolymers; D018832:Molecular Chaperones; C487896:GSTK1 protein, human; D005982:Glutathione Transferase