4-Hydroxy-2-nonenal induces endothelial cell injury via PKCdelta and biphasic JNK activation

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dc.contributor.authorGoya, Sho
dc.contributor.authorHirata, Haruhiko
dc.contributor.authorHoshino, Shigenori
dc.contributor.authorInoue, Koji
dc.contributor.authorKashiwa, Yozo
dc.contributor.authorKawase, Ichiro
dc.contributor.authorKijima, Takashi
dc.contributor.authorKumagai, Toru
dc.contributor.authorMayumi, Masahiko
dc.contributor.authorOsaki, Tadashi
dc.contributor.authorSuzuki, Mayumi
dc.contributor.authorTachibana, Isao
dc.contributor.authorTakeda, Yoshito
dc.contributor.authorTakimoto, Takayuki
dc.contributor.authorYano, Yukihiro
dc.contributor.authorYoshida, Yoshida
dc.date.accessioned2008-06-18T08:03:44Z
dc.date.available2008-06-18T08:03:44Z
dc.date.issued2008-03-10
dc.description.abstract4-Hydroxy-2-nonenal (4-HNE), a major product generated during oxidative stress, exhibits cytotoxic effects; however, the mechanisms of 4-HNE-induced endothelial cell injury are not well defined. To explore this issue, we examined how 4-HNE damages human umbilical vein endothelial cells (HUVECs) and found that 4-HNE induced biphasic activation of c-Jun N-terminal kinase (JNK). Both pre- and post-treatment of HUVECs with SP600125, a specific JNK inhibitor, significantly suppressed the cytotoxic effects of 4-HNE. Inhibition of protein kinase Cd (PKCd), which was also phosphorylated by 4-HNE, reduced endothelial cell injury as well as late-phase JNK phosphorylation elicited by 4-HNE. Inversely, pre-treatment of HUVECs with SP600125 suppressed PKCd activation. Taken together, these results support the concept that 4-HNE induces vascular endothelial cell injury by the interaction between biphasic JNK activation and the PKCd pathway.en
dc.identifier.issn1611-2156
dc.identifier.urihttp://hdl.handle.net/2003/25697
dc.identifier.urihttp://dx.doi.org/10.17877/DE290R-8112
dc.language.isoende
dc.relation.ispartofseriesEXCLI Journal ; Vol. 7, 2008de
dc.subject4-Hydroxy-2-nonenalen
dc.subjectCden
dc.subjectcell injuryen
dc.subjectc-Jun N-terminal kinaseen
dc.subjectendothelial cellen
dc.subjectkinaseen
dc.subjectoxidative stressen
dc.subjectproteinen
dc.subject.ddc610
dc.title4-Hydroxy-2-nonenal induces endothelial cell injury via PKCdelta and biphasic JNK activationen
dc.typeTextde
dc.type.publicationtypearticlede
dcterms.accessRightsopen access
eldorado.dnb.zdberstkatid2132560-1

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