Authors: Goya, Sho
Hirata, Haruhiko
Hoshino, Shigenori
Inoue, Koji
Kashiwa, Yozo
Kawase, Ichiro
Kijima, Takashi
Kumagai, Toru
Mayumi, Masahiko
Osaki, Tadashi
Suzuki, Mayumi
Tachibana, Isao
Takeda, Yoshito
Takimoto, Takayuki
Yano, Yukihiro
Yoshida, Yoshida
Title: 4-Hydroxy-2-nonenal induces endothelial cell injury via PKCdelta and biphasic JNK activation
Language (ISO): en
Abstract: 4-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.
Subject Headings: 4-Hydroxy-2-nonenal
cell injury
c-Jun N-terminal kinase
endothelial cell
oxidative stress
Issue Date: 2008-03-10
Appears in Collections:Original Articles

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