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Article: Adiponectin-induced endothelial nitric oxide synthase activation and nitric oxide production are mediated by APPL1 in endothelial cells

TitleAdiponectin-induced endothelial nitric oxide synthase activation and nitric oxide production are mediated by APPL1 in endothelial cells
Authors
Issue Date2007
PublisherAmerican Diabetes Association. The Journal's web site is located at http://diabetes.diabetesjournals.org/
Citation
Diabetes, 2007, v. 56 n. 5, p. 1387-1394 How to Cite?
AbstractAdiponectin protects the vascular system partly through stimulation of endothelial nitric oxide (NO) production and endothelium-dependent vasodilation. The current study investigated the role of two recently identified adiponectin receptors, AdipoR1 and -R2, and their downstream effectors in mediating the endothelium actions of adiponectin. In human umbilical vein endothelial cells, adiponectin-induced phosphorylation of endothelial NO synthase (eNOS) at Ser 1177 and NO production were abrogated when expression of AdipoR1 and -R2 were simultaneously suppressed. Proteomic analysis demonstrated that the cytoplasmic tails of both AdipoR1 and -R2 interacted with APPL1, an adaptor protein that contains a PH (pleckstrin homology) domain, a PTB (phosphotyrosine-binding) domain, and a Leucine zipper motif. Suppression of APPL1 expression by RNA interference significantly attenuated adiponectin-induced phosphorylation of AMP-activated protein kinase (AMPK) at Thr 172 and eNOS at Ser 1177, and the complex formation between eNOS and heat shock protein 90, resulting in a marked reduction of NO production. Adenovirus-mediated overexpression of a constitutively active version of AMPK reversed these changes. In db/db diabetic mice, both APPL1 expression and adiponectin-induced vasodilation were significantly decreased compared with their lean littermates. Taken together, these results suggest that APPL1 acts as a common downstream effector of AdipoR1 and -R2, mediating adiponectin-evoked endothelial NO production and endothelium-dependent vasodilation. © 2007 by the American Diabetes Association.
Persistent Identifierhttp://hdl.handle.net/10722/163076
ISSN
2015 Impact Factor: 8.784
2015 SCImago Journal Rankings: 5.185
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorCheng, KKYen_HK
dc.contributor.authorLam, KSLen_HK
dc.contributor.authorWang, Yen_HK
dc.contributor.authorHuang, Yen_HK
dc.contributor.authorCarling, Den_HK
dc.contributor.authorWu, Den_HK
dc.contributor.authorWong, Cen_HK
dc.contributor.authorXu, Aen_HK
dc.date.accessioned2012-09-05T05:27:17Z-
dc.date.available2012-09-05T05:27:17Z-
dc.date.issued2007en_HK
dc.identifier.citationDiabetes, 2007, v. 56 n. 5, p. 1387-1394en_HK
dc.identifier.issn0012-1797en_HK
dc.identifier.urihttp://hdl.handle.net/10722/163076-
dc.description.abstractAdiponectin protects the vascular system partly through stimulation of endothelial nitric oxide (NO) production and endothelium-dependent vasodilation. The current study investigated the role of two recently identified adiponectin receptors, AdipoR1 and -R2, and their downstream effectors in mediating the endothelium actions of adiponectin. In human umbilical vein endothelial cells, adiponectin-induced phosphorylation of endothelial NO synthase (eNOS) at Ser 1177 and NO production were abrogated when expression of AdipoR1 and -R2 were simultaneously suppressed. Proteomic analysis demonstrated that the cytoplasmic tails of both AdipoR1 and -R2 interacted with APPL1, an adaptor protein that contains a PH (pleckstrin homology) domain, a PTB (phosphotyrosine-binding) domain, and a Leucine zipper motif. Suppression of APPL1 expression by RNA interference significantly attenuated adiponectin-induced phosphorylation of AMP-activated protein kinase (AMPK) at Thr 172 and eNOS at Ser 1177, and the complex formation between eNOS and heat shock protein 90, resulting in a marked reduction of NO production. Adenovirus-mediated overexpression of a constitutively active version of AMPK reversed these changes. In db/db diabetic mice, both APPL1 expression and adiponectin-induced vasodilation were significantly decreased compared with their lean littermates. Taken together, these results suggest that APPL1 acts as a common downstream effector of AdipoR1 and -R2, mediating adiponectin-evoked endothelial NO production and endothelium-dependent vasodilation. © 2007 by the American Diabetes Association.en_HK
dc.languageengen_US
dc.publisherAmerican Diabetes Association. The Journal's web site is located at http://diabetes.diabetesjournals.org/en_HK
dc.relation.ispartofDiabetesen_HK
dc.subject.meshAmp-Activated Protein Kinasesen_US
dc.subject.meshAdaptor Proteins, Signal Transducingen_US
dc.subject.meshAdiponectin - Pharmacologyen_US
dc.subject.meshApoptosis - Drug Effects - Physiologyen_US
dc.subject.meshCarrier Proteins - Geneticsen_US
dc.subject.meshCells, Cultureden_US
dc.subject.meshEndothelium, Vascular - Drug Effects - Enzymology - Physiologyen_US
dc.subject.meshEnzyme Activation - Drug Effectsen_US
dc.subject.meshGenetic Vectorsen_US
dc.subject.meshHumansen_US
dc.subject.meshIsometric Contraction - Drug Effects - Physiologyen_US
dc.subject.meshMultienzyme Complexes - Genetics - Metabolismen_US
dc.subject.meshNitric Oxide - Biosynthesisen_US
dc.subject.meshNitric Oxide Synthase Type Iii - Drug Effects - Metabolismen_US
dc.subject.meshProtein-Serine-Threonine Kinases - Genetics - Metabolismen_US
dc.subject.meshReceptors, Adiponectinen_US
dc.subject.meshReceptors, Cell Surface - Geneticsen_US
dc.subject.meshRecombinant Fusion Proteins - Metabolismen_US
dc.subject.meshUmbilical Veinsen_US
dc.subject.meshVasodilation - Drug Effects - Physiologyen_US
dc.titleAdiponectin-induced endothelial nitric oxide synthase activation and nitric oxide production are mediated by APPL1 in endothelial cellsen_HK
dc.typeArticleen_HK
dc.identifier.emailCheng, KKY: dorncky@hkucc.hku.hken_HK
dc.identifier.emailLam, KSL: ksllam@hku.hken_HK
dc.identifier.emailWang, Y: yuwanghk@hku.hken_HK
dc.identifier.emailXu, A: amxu@hkucc.hku.hken_HK
dc.identifier.authorityCheng, KKY=rp01672en_HK
dc.identifier.authorityLam, KSL=rp00343en_HK
dc.identifier.authorityWang, Y=rp00239en_HK
dc.identifier.authorityXu, A=rp00485en_HK
dc.description.naturelink_to_OA_fulltexten_US
dc.identifier.doi10.2337/db06-1580en_HK
dc.identifier.pmid17287464en_HK
dc.identifier.scopuseid_2-s2.0-34248147538en_HK
dc.identifier.hkuros126067-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-34248147538&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume56en_HK
dc.identifier.issue5en_HK
dc.identifier.spage1387en_HK
dc.identifier.epage1394en_HK
dc.identifier.eissn1939-327X-
dc.identifier.isiWOS:000246291500024-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridCheng, KKY=7402997599en_HK
dc.identifier.scopusauthoridLam, KSL=8082870600en_HK
dc.identifier.scopusauthoridWang, Y=34973733700en_HK
dc.identifier.scopusauthoridHuang, Y=34770945300en_HK
dc.identifier.scopusauthoridCarling, D=7005899093en_HK
dc.identifier.scopusauthoridWu, D=7404297751en_HK
dc.identifier.scopusauthoridWong, C=35148671700en_HK
dc.identifier.scopusauthoridXu, A=7202655409en_HK
dc.identifier.citeulike4498369-

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