File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: A disulfide-bond A oxidoreductase-like protein (DsbA-L) regulates adiponectin multimerization

TitleA disulfide-bond A oxidoreductase-like protein (DsbA-L) regulates adiponectin multimerization
Authors
Issue Date2008
PublisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.org
Citation
Proceedings Of The National Academy Of Sciences Of The United States Of America, 2008, v. 105 n. 47, p. 18302-18307 How to Cite?
AbstractImpairments 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 TNFα. 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. © 2008 by The National Academy of Sciences of the USA.
Persistent Identifierhttp://hdl.handle.net/10722/163218
ISSN
2015 Impact Factor: 9.423
2015 SCImago Journal Rankings: 6.883
ISI Accession Number ID
Funding AgencyGrant Number
National Institutes of HealthDK76902
DK69930
Hong Kong Research Grant CouncilCRF 2/07C
Funding Information:

We thank Dr. Wenhong Cao (The Hamner Institute for Health Science, Research) for providing WAT from ND- or HFD-fed mice. This work wassupported by grants from the National Institutes of Health (DK76902, to F.L.; and DK69930, to L.Q.D.) and Hong Kong Research Grant Council (CRF 2/07C, to AX).

References

 

DC FieldValueLanguage
dc.contributor.authorLiu, Men_US
dc.contributor.authorZhou, Len_US
dc.contributor.authorXu, Aen_US
dc.contributor.authorLam, KSLen_US
dc.contributor.authorWetzel, MDen_US
dc.contributor.authorXiang, Ren_US
dc.contributor.authorZhang, Jen_US
dc.contributor.authorXin, Xen_US
dc.contributor.authorDong, LQen_US
dc.contributor.authorLiu, Fen_US
dc.date.accessioned2012-09-05T05:28:50Z-
dc.date.available2012-09-05T05:28:50Z-
dc.date.issued2008en_US
dc.identifier.citationProceedings Of The National Academy Of Sciences Of The United States Of America, 2008, v. 105 n. 47, p. 18302-18307en_US
dc.identifier.issn0027-8424en_US
dc.identifier.urihttp://hdl.handle.net/10722/163218-
dc.description.abstractImpairments 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 TNFα. 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. © 2008 by The National Academy of Sciences of the USA.en_US
dc.languageengen_US
dc.publisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.orgen_US
dc.relation.ispartofProceedings of the National Academy of Sciences of the United States of Americaen_US
dc.subject.mesh3T3-L1 Cellsen_US
dc.subject.meshAdiponectin - Chemistry - Metabolism - Secretionen_US
dc.subject.meshAdulten_US
dc.subject.meshAnimalsen_US
dc.subject.meshBiocatalysisen_US
dc.subject.meshBiopolymers - Chemistryen_US
dc.subject.meshCase-Control Studiesen_US
dc.subject.meshElectrophoresis, Polyacrylamide Gelen_US
dc.subject.meshFemaleen_US
dc.subject.meshGlutathione Transferase - Metabolism - Physiologyen_US
dc.subject.meshHumansen_US
dc.subject.meshMaleen_US
dc.subject.meshMiceen_US
dc.subject.meshMice, Inbred Balb Cen_US
dc.subject.meshMiddle Ageden_US
dc.subject.meshMolecular Chaperones - Metabolism - Physiologyen_US
dc.subject.meshObesity - Metabolismen_US
dc.subject.meshProtein Foldingen_US
dc.subject.meshProtein Processing, Post-Translationalen_US
dc.subject.meshRna Interferenceen_US
dc.subject.meshTranscription, Geneticen_US
dc.subject.meshTwo-Hybrid System Techniquesen_US
dc.titleA disulfide-bond A oxidoreductase-like protein (DsbA-L) regulates adiponectin multimerizationen_US
dc.typeArticleen_US
dc.identifier.emailXu, A:amxu@hkucc.hku.hken_US
dc.identifier.emailLam, KSL:ksllam@hku.hken_US
dc.identifier.authorityXu, A=rp00485en_US
dc.identifier.authorityLam, KSL=rp00343en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1073/pnas.0806341105en_US
dc.identifier.pmid19011089en_US
dc.identifier.scopuseid_2-s2.0-57449111690en_US
dc.identifier.hkuros154211-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-57449111690&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume105en_US
dc.identifier.issue47en_US
dc.identifier.spage18302en_US
dc.identifier.epage18307en_US
dc.identifier.isiWOS:000261489300049-
dc.publisher.placeUnited Statesen_US
dc.identifier.f10001131889-
dc.identifier.scopusauthoridLiu, M=16233590900en_US
dc.identifier.scopusauthoridZhou, L=35274069900en_US
dc.identifier.scopusauthoridXu, A=7202655409en_US
dc.identifier.scopusauthoridLam, KSL=8082870600en_US
dc.identifier.scopusauthoridWetzel, MD=36003271800en_US
dc.identifier.scopusauthoridXiang, R=7006818699en_US
dc.identifier.scopusauthoridZhang, J=22735803600en_US
dc.identifier.scopusauthoridXin, X=36872878400en_US
dc.identifier.scopusauthoridDong, LQ=7402561181en_US
dc.identifier.scopusauthoridLiu, F=36064205800en_US

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats