15-Deoxy-delta12,14-prostaglandin J2, a neuroprotectant or a neurotoxicant?

Redox Regulation of Soluble Epoxide Hydrolase by 15-Deoxy-Δ-Prostaglandin J 2 Controls Coronary Hypoxic Vasodilation

“…The disease-limiting affects of 15d-PGJ 2 is likely significantly mediated via by its inhibition of sEH, consistent with the overlapping cytoprotection provided by established hydrolase antagonists. Thus 15d-PGJ 2 protects against cancer, 9 inflammation and hypertension, 4 and diseases of the brain, 10 gut, 11 heart, 12 and lungs. 13 sEH inhibitors provide an integrated cardiovascular protection against hypertension, ischemia and reperfusion, hypertrophy, and heart failure.…”

Anti-heat Shock 70 kDa Protein Antibody Induced Neuronal Cell Death

“…44) 15d-PGJ 2 increases ROS at neurotoxic concentrations. 21) Similarly, anti-Hsp70 antibody generated ROS in a concentrationdependent manner. The plasmalemmal Hsp70 is targeted for autoantibodies against Hsp70, which are upregulated in neurologic diseases such as stroke.…”

“…21) We examined effects of 15d-PGJ 2 on the anti-Hsp70 antibody-induced neuronal cell death. Cortical neurons were treated with 50 ng/mL goat IgG or anti-Hsp70 antibody in the absence or presence of 3.5 µM 15d-PGJ 2 for 48 h. The value of EC 50 of 15d-PGJ 2 against neuronal cells was about 3.5 µM in the presence of serum.…”

“…21) Its nuclear receptor, peroxisome proliferators-activated receptor γ (PPARγ) is involved in the neuroprotective effect of 15d-PGJ 2 . 22) Neither PPARγ nor its membrane receptor, chemoattractant receptor homologous molecule expressed on T-helper 2 (Th2) cells (CRTH2), was involved in 15d-PGJ 2 -induced neurotoxicity.…”

Pharmacological Enhancement of Neuronal Survival

“…Several reports have indicated that the prostaglandin 15-deoxy-delta-12,14-prostaglandin J2 (15d-PGJ2) displays both neuroprotective (Aoun et al, 2003;Heneka et al, 1999;Zhuang et al, 2003) and neurotoxic effects (Li et al, 2004a(Li et al, , 2004b. Since 15d-PGJ2-induced effects on DNA synthesis in vascular smooth muscle were dependent on phosphatidyl inositol 3-kinase (P13-k), and PB-k can enhance the expression of antiapoptotic proteins and inhibit the activity of proapoptotic ones (Cantley, 2002;Cantrell, 2001;Doble and Woodgett, 2003;Kirschenbaum et al, 2001;Koh et al, 2003Koh et al, , 2004Koh et al, , 2006Pap and Cooper, 1998;Sang et al, 2001), Koh et al (2006) assessed the effects of 15d-PGJ2 on free radical formation, membrane lipid peroxidation, and cellular signals such as P13-k, AK+, and markers of apoptosis in N/8D3 neuronal cells (i.e., a hybrid neuron line obtained by the fusion of dorsal root ganglion neuron isolated from 4-week-old BALB/c mice with the mouse neuroblastoma N18TH2 cells) over a broad dose range.…”