15-deoxy-Delta(12,14)-prostaglandin J2 induces vascular endothelial cell apoptosis through the sequential activation of MAPKS and p53.

The Journal of Biological Chemistry
Tsung-Chuan HoYeou-Ping Tsao

Abstract

15-Deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) is a potent anti-angiogenic factor and induces endothelial cell apoptosis, although the mechanism remains unclear. In this study, 15d-PGJ(2) was found to increase p53 levels of the human umbilical vein endothelial cells by stabilizing p53. Both 15d-PGJ(2)-induced apoptosis and the induction of p21(Waf1) and Bax can be abolished by p53 small interfering RNA but not by peroxisome proliferator-activated receptor gamma inhibitors. Moreover, 15d-PGJ(2) activated JNK and p38 MAPK while inducing p53 phosphorylation at sites responsible for p53 activity. JNK inhibitor (SP600125) or p38 MAPK inhibitor (SB203580) pretreatment attenuated 15d-PGJ(2)-mediated apoptosis and suppressed the p21(Waf1) and Bax expressions without affecting p53 protein accumulation. Pretreatment with SP600125 partially prevented the phosphorylation of p53 at serines 33 and 392 induced by 15d-PGJ(2). 15d-PGJ(2) was also found to induce reactive oxygen species generation and partially blocked nuclear factor-kappaB activity. Pretreatment with antioxidant N-acetylcysteine prevented the p53 accumulation, the phosphorylations of JNK and p38 MAPK, the inhibition of NF-kappaB activity, as well as the apoptosis induced...Continue Reading

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Citations

Apr 1, 2014·Prostaglandins & Other Lipid Mediators·Yukiko SakabaYasuharu Tanaka
Jun 17, 2010·Physiology·Nicolas Rotman, Walter Wahli
Jun 5, 2015·American Journal of Physiology. Cell Physiology·Tsung-Chuan HoYeou-Ping Tsao
Apr 22, 2015·Molecular and Cellular Biochemistry·Bing QinZhengqi Lu
Jul 28, 2020·Prostaglandins, Leukotrienes, and Essential Fatty Acids·Youjia DuPeter Zahradka
Oct 6, 2009·Biochemical and Biophysical Research Communications·Asako HironakaYasuharu Tanaka

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