Show simple item record

dc.contributor.authorMora-Pale, M.
dc.contributor.authorKwon, S.J.
dc.contributor.authorLinhardt, Robert J.
dc.contributor.authorDordick, J.S.
dc.date2012
dc.date.accessioned2022-06-23T04:11:25Z
dc.date.available2022-06-23T04:11:25Z
dc.date.issued2012
dc.identifier.citationTrimer hydroxylated quinone (IIIHyQ) derived from apocynin targets cysteine residues of p47phox preventing the activation of human vascular NADPH oxidase, M.Mora-Pale, S.J. Kwon, R. J. Linhardt, J. S. Dordick, Free Radical Biology and Medicine, 52, 962-969, 2012.
dc.identifier.urihttps://hdl.handle.net/20.500.13015/5269
dc.identifier.urihttps://doi.org/10.1016/j.freeradbiomed.2011.12.015
dc.descriptionFree Radical Biology and Medicine, 52, 962-969
dc.descriptionNote : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
dc.description.abstractEnzymatically derived oligophenols from apocynin can be effective inhibitors of human vascular NADPH oxidase (Nox). An isolated trimer hydroxylated quinone (IIIHyQ) has been shown to inhibit endothelial NADPH oxidase with an IC(50) ~30 nM. In vitro studies demonstrated that IIIHyQ is capable of disrupting the interaction between p47(phox) and p22(phox), thereby blocking the activation of the Nox2 isoform. Herein, we report the role of key cysteine residues in p47(phox) as targets for the IIIHyQ. Incubation of p47(phox) with IIIHyQ results in a decrease of ~80% of the protein free cysteine residues; similar results were observed using 1,2- and 1,4-naphthoquinones, whereas apocynin was unreactive. Mutants of p47(phox), in which each Cys was individually replaced by Ala (at residues 111, 196, and 378) or Gly (at residue 98), were generated to evaluate their individual importance in IIIHyQ-mediated inhibition of p47(phox) interaction with p22(phox). Specific Michael addition on Cys196, within the N-SH3 domain, by the IIIHyQ is critical for disrupting the p47(phox)-p22(phox) interaction. When a C196A mutation was tested, the IIIHyQ was unable to disrupt the p47(phox)-p22(phox) interaction. However, the IIIHyQ was effective at disrupting this interaction with the other mutants, displaying IC(50) values (4.9, 21.0, and 2.3μM for the C111A, C378A, and C98G mutants, respectively) comparable to that of wild-type p47(phox).
dc.languageen_US
dc.language.isoENG
dc.publisherElsevier
dc.relation.ispartofThe Linhardt Research Labs Online Collection
dc.relation.ispartofRensselaer Polytechnic Institute, Troy, NY
dc.relation.urihttps://harc.rpi.edu/
dc.subjectBiology
dc.subjectChemistry and chemical biology
dc.subjectChemical and biological engineering
dc.subjectBiomedical engineering
dc.titleTrimer hydroxylated quinone (IIIHyQ) derived from apocynin targets cysteine residues of p47phox preventing the activation of human vascular NADPH oxidase
dc.typeArticle
dcterms.accessRightsA full text version is available in DSpace@RPI
dcterms.isVersionOfhttps://doi.org/10.1016/j.freeradbiomed.2011.12.015
dc.rights.holderIn Copyright : this Item is protected by copyright and/or related rights. You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s). https://rightsstatements.org/page/InC/1.0/
dc.creator.identifierhttps://orcid.org/0000-0003-2219-5833
dc.relation.departmentThe Linhardt Research Labs.
dc.relation.departmentThe Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record