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Article: Oxidized low-density lipoprotein activates p66shc via lectin-like oxidized low-density lipoprotein receptor-1, protein kinase c-β, and c-jun n-terminal kinase kinase in human endothelial cells

TitleOxidized low-density lipoprotein activates p66shc via lectin-like oxidized low-density lipoprotein receptor-1, protein kinase c-β, and c-jun n-terminal kinase kinase in human endothelial cells
Authors
Keywordsendothelium
lipoproteins
reactive oxygen species
Issue Date2011
PublisherLippincott Williams & Wilkins. The Journal's web site is located at http://www.lww.com/product/?1079-5642
Citation
Arteriosclerosis, Thrombosis, And Vascular Biology, 2011, v. 31 n. 9, p. 2090-2097 How to Cite?
AbstractObjective-: Deletion of the mitochondrial gene p66 protects from endothelial dysfunction and atherosclerotic plaque formation in mice fed a high-fat diet. However, the molecular mechanisms underlying this beneficial effect have not yet been delineated. The present study was designed to elucidate the proatherogenic mechanisms by which p66 mediates oxidized low-density lipoprotein (oxLDL) uptake by the endothelium, a critical step in plaque formation. Methods and results-: Incubation of human aortic endothelial cells with oxLDL led to phosphorylation of p66 at Ser36. Inhibition of lectin-like oxLDL receptor-1 prevented p66 phosphorylation, confirming that this effect is mediated by lectin-like oxLDL receptor-1. OxLDL also increased phosphorylation of protein kinase C β2 (PKCβ2) at both Thr641 and Ser660, as well as c-Jun N-terminal kinase (JNK). Furthermore, inhibition of PKCβ2 prevented the activation of JNK, suggesting that PKCβ2 is upstream of JNK. Finally, p66 silencing blunted oxLDL-induced O2 production, underscoring the critical role of p66 in oxLDL-induced oxidative stress in endothelial cells. Conclusion-: In this study we provide the molecular mechanisms mediating the previously observed atherogenic properties of p66. Taken together, our data set the stage for the design of novel therapeutic tools to retard atherogenesis through the inhibition of p66. © 2011 American Heart Association. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/139602
ISSN
2014 Impact Factor: 6.000
2014 SCImago Journal Rankings: 2.980
ISI Accession Number ID
Funding AgencyGrant Number
Swiss National Research Foundation3100-06811802/1
3100-30130500
Swiss Heart Foundation
MERCATOR Schweiz Foundation
Fondazione Roma, Italy
strategic alliance of Pfizer, New York
Funding Information:

This study was supported by grants from the Swiss National Research Foundation (Grant 3100-06811802/1 to T.F.L., Grant 3100-30130500 to G.G.C.); the Swiss Heart Foundation; the MERCATOR Schweiz Foundation; and the Fondazione Roma, Italy (to F.C.) and by a strategic alliance of Pfizer, New York.

References

 

DC FieldValueLanguage
dc.contributor.authorShi, Yen_HK
dc.contributor.authorCosentino, Fen_HK
dc.contributor.authorCamici, GGen_HK
dc.contributor.authorAkhmedov, Aen_HK
dc.contributor.authorVanhoutte, PMen_HK
dc.contributor.authorTanner, FCen_HK
dc.contributor.authorLüscher, TFen_HK
dc.date.accessioned2011-09-23T05:52:27Z-
dc.date.available2011-09-23T05:52:27Z-
dc.date.issued2011en_HK
dc.identifier.citationArteriosclerosis, Thrombosis, And Vascular Biology, 2011, v. 31 n. 9, p. 2090-2097en_HK
dc.identifier.issn1079-5642en_HK
dc.identifier.urihttp://hdl.handle.net/10722/139602-
dc.description.abstractObjective-: Deletion of the mitochondrial gene p66 protects from endothelial dysfunction and atherosclerotic plaque formation in mice fed a high-fat diet. However, the molecular mechanisms underlying this beneficial effect have not yet been delineated. The present study was designed to elucidate the proatherogenic mechanisms by which p66 mediates oxidized low-density lipoprotein (oxLDL) uptake by the endothelium, a critical step in plaque formation. Methods and results-: Incubation of human aortic endothelial cells with oxLDL led to phosphorylation of p66 at Ser36. Inhibition of lectin-like oxLDL receptor-1 prevented p66 phosphorylation, confirming that this effect is mediated by lectin-like oxLDL receptor-1. OxLDL also increased phosphorylation of protein kinase C β2 (PKCβ2) at both Thr641 and Ser660, as well as c-Jun N-terminal kinase (JNK). Furthermore, inhibition of PKCβ2 prevented the activation of JNK, suggesting that PKCβ2 is upstream of JNK. Finally, p66 silencing blunted oxLDL-induced O2 production, underscoring the critical role of p66 in oxLDL-induced oxidative stress in endothelial cells. Conclusion-: In this study we provide the molecular mechanisms mediating the previously observed atherogenic properties of p66. Taken together, our data set the stage for the design of novel therapeutic tools to retard atherogenesis through the inhibition of p66. © 2011 American Heart Association. All rights reserved.en_HK
dc.languageengen_US
dc.publisherLippincott Williams & Wilkins. The Journal's web site is located at http://www.lww.com/product/?1079-5642en_HK
dc.relation.ispartofArteriosclerosis, Thrombosis, and Vascular Biologyen_HK
dc.rightsThis is a non-final version of an article published in final form in (provide complete journal citation)-
dc.subjectendotheliumen_HK
dc.subjectlipoproteinsen_HK
dc.subjectreactive oxygen speciesen_HK
dc.subject.meshEndothelial Cells - metabolism-
dc.subject.meshJNK Mitogen-Activated Protein Kinases - metabolism-
dc.subject.meshLipoproteins, LDL - physiology-
dc.subject.meshProtein Kinase C - metabolism-
dc.subject.meshScavenger Receptors, Class E - metabolism-
dc.titleOxidized low-density lipoprotein activates p66shc via lectin-like oxidized low-density lipoprotein receptor-1, protein kinase c-β, and c-jun n-terminal kinase kinase in human endothelial cellsen_HK
dc.typeArticleen_HK
dc.identifier.emailVanhoutte, PM: vanhoutt@hku.hken_HK
dc.identifier.authorityVanhoutte, PM=rp00238en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1161/ATVBAHA.111.229260en_HK
dc.identifier.pmid21817106en_HK
dc.identifier.scopuseid_2-s2.0-80052175705en_HK
dc.identifier.hkuros195639en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-80052175705&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume31en_HK
dc.identifier.issue9en_HK
dc.identifier.spage2090en_HK
dc.identifier.epage2097en_HK
dc.identifier.isiWOS:000293955200028-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridShi, Y=7404963998en_HK
dc.identifier.scopusauthoridCosentino, F=7006332290en_HK
dc.identifier.scopusauthoridCamici, GG=7005597818en_HK
dc.identifier.scopusauthoridAkhmedov, A=7005839303en_HK
dc.identifier.scopusauthoridVanhoutte, PM=7202304247en_HK
dc.identifier.scopusauthoridTanner, FC=7005433148en_HK
dc.identifier.scopusauthoridLüscher, TF=18935805600en_HK

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