Goya, ShoHirata, HaruhikoHoshino, ShigenoriInoue, KojiKashiwa, YozoKawase, IchiroKijima, TakashiKumagai, ToruMayumi, MasahikoOsaki, TadashiSuzuki, MayumiTachibana, IsaoTakeda, YoshitoTakimoto, TakayukiYano, YukihiroYoshida, Yoshida2008-06-182008-06-182008-03-101611-2156http://hdl.handle.net/2003/2569710.17877/DE290R-81124-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.enEXCLI Journal ; Vol. 7, 20084-Hydroxy-2-nonenalCdcell injuryc-Jun N-terminal kinaseendothelial cellkinaseoxidative stressprotein610article (journal)