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 Cd cell injury c-Jun N-terminal kinase endothelial cell kinase oxidative stress protein |
URI: | http://hdl.handle.net/2003/25697 http://dx.doi.org/10.17877/DE290R-8112 |
Issue Date: | 2008-03-10 |
Appears in Collections: | Original Articles |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
yoshida10-03proof.pdf | DNB | 325.59 kB | Adobe PDF | View/Open |
This item is protected by original copyright |
This item is protected by original copyright rightsstatements.org