Disease relevance of Dddd-PGD2

• We examined the protective effects of cycloheximide against cytotoxicity induced by vincristine, colchicine, delta 12-prostaglandin J2, or other antitumor agents on the human osteosarcoma cell line, KSu [1].
• The possibility that hsp70 could play a role in the control of rhinovirus replication is suggested by the fact that a different class of HSP inducers, the cyclopentenone prostaglandins PGA1 and delta 12-PGJ2, were also effective in inhibiting HRV replication in HeLa cells [2].
• Using a human neuroblastoma cell line GOTO, the effects of delta 12-prostaglandin (PG) J2 on the modulation of cell cycle progression and protein synthesis were examined in comparison with those caused by heat shock (HS). delta 12-PGJ2 induced G1 arrest, the peak of which was obtained at 24 h and continued for 72 h [3].
• Dot blot hybridization analysis revealed that delta 7-PGA1 and delta 12-PGJ2 inhibited the primary transcription of HSV-2 [4].
• Mechanism of inhibition of herpes simplex virus replication by delta 7-prostaglandin A1 and delta 12-prostaglandin J2 [4].

High impact information on Dddd-PGD2

• This report describes the preferential binding of the growth inhibitory prostaglandins by L-FABP and the reversible inhibition of thymidine incorporation into DNA by PGA2 and delta 12-PGJ2 in primary cultures of purified rat hepatocytes [5].
• Prostaglandin D2 has been shown to have growth inhibitory properties in several malignant cell lines. delta 12-Prostaglandin-J2 (delta 12-PG J2) is a derivative of prostaglandin D2 that has been shown to have similar inhibitory properties [6].
• In plasma, PGD(2) is rapidly transformed into its major metabolite delta(12)-PGJ(2), the effect of which on eosinophil migration has not yet been characterized [7].
• Desensitization studies using calcium flux suggested that delta(12)-PGJ(2) signaled through the same receptor, CRTH2, as PGD(2) [7].
• Finally, delta(12)-PGJ(2) was able to mobilize mature eosinophils from the bone marrow of the guinea pig isolated perfused hind limb [7].

Chemical compound and disease context of Dddd-PGD2

• The antitumor activity of delta 7-prostaglandin A1 (delta 7-PGA1) or delta 12-prostaglandin J2 (delta 12-PGJ2) on human ovarian cancer cell lines resistant to cisplatin (CDDP), doxorubicin (ADR), and L-phenylalanine mustard (l-PAM) was studied in vitro [8].
• delta 12-Prostaglandin J2 (delta 12-PGJ2), a naturally occurring dehydration product of prostaglandin D2, is shown to suppress the replication of vesicular stomatitis virus (VSV) in two different epithelial monkey cell lines [9].
• These results suggest that delta 12-PGJ2 suppresses not only cell growth but also expression of the AFP gene and the albumin gene at the transcriptional level in human hepatoma cells [10].

Biological context of Dddd-PGD2

• When delta 12-PGJ2 was incubated with G2/M phase cells, it induced only a small and transient increase in the 68-kDa proteins [11].
• From functional analysis of various deletion mutant genes we found that the delta 12-PGJ2-responsive element was localized in a region from -690 to -660, containing an E-box motif, which was essential for the delta 12-PGJ2-stimulated promoter activity [12].
• Cyclopentenone prostaglandins (PGs) such as PGA2 and delta 12-PGJ2 act specifically on cells in the G1 phase and induce block of cell cycle progression (Ohno, K., Sakai, T., Fukushima, M., Narumiya, S., and Fujiwara, M. (1988) J. Pharmacol. Exp. Ther. 245, 294-298) [11].
• These results indicate that delta 12-PGJ2 induces the expression of the rat HO-1 gene through nuclear protein binding to a specific element having an E-box motif [12].
• When the region containing the delta 12-PGJ2-responsive element was combined with a heterologous promoter, SV40 promoter, in the sense and antisense direction, the element showed an enhancer activity in response to delta 12-PGJ2 [12].

Anatomical context of Dddd-PGD2

• Cyclopentenone prostaglandins (PG) such as delta 12-PGJ2 and PGA are potent inhibitors of growth in a variety of cultured cells, including human epidermal cells [13].
• To clarify the mechanism of PG cytotoxicity in human epidermal cells, we examined the effects of delta 12-PGJ2 on the induction of a heat shock protein (HSP), and on the organization of cytoskeletons in the HSC-I-transformed human epidermal cell line [13].
• These results suggest that exposure of keratinocytes to stressors such as delta 12-PGJ2 and ultraviolet light increases the binding sites for U1RNP,SS-A/Ro, and SS-B/La antibodies [14].
• Addition of delta 12-PGJ2 to confluent HSC-1 cells resulted in the disappearance of actin filaments and the disarrangement of keratin filaments, as visualized with fluorescent-labeled phallacidine or immunofluorescence [13].
• Inhibitory effect of an intracellular glutathione on delta 12-prostaglandin J2-induced protein syntheses in porcine aortic endothelial cells [15].

Associations of Dddd-PGD2 with other chemical compounds

• PGD2 induces sleep, regulates nociception, inhibits platelet aggregation, acts as an allergic mediator, and is further converted to 9 alpha, 11 beta-PGF2 or the J series of prostanoids, such as PGJ2, delta 12-PGJ2, and 15-deoxy-delta 12,14-PGJ2 [16].
• Cycloheximide blocked the DNA fragmentation and morphological changes induced by delta 12-PGJ2 [17].
• Furthermore, GSH strongly inhibited the in vitro binding of delta 12-PGJ2 to isolated nuclei, which is N-ethylmaleimide sensitive [15].
• On the other hand, more than 70% of delta 12-PGJ2-derived nuclear radioactivity was associated with the residues and resistant to extraction with acidic ethyl acetate [18].
• Prostaglandin A2 and delta 12-prostaglandin J2 induce apoptosis in L1210 cells [17].

Gene context of Dddd-PGD2

• We have developed a highly sensitive and specific solid-phase enzyme immunoassay for 9-deoxy-delta 9,delta 12-dihydroprostaglandin D2 (delta 12-PGJ2) and studied the occurrence of this novel PGD2 metabolite in human urine [19].
• Identification of a cis-regulatory element for delta 12-prostaglandin J2-induced expression of the rat heme oxygenase gene [12].
• Following treatment with 5 micrograms/ml of delta 12-PGJ2, however, HSP72 was found in the nucleolus as well as in the cytoplasm [13].
• PGA1 and delta 12-PGJ2 were found to induce HSP70 synthesis in uninfected or VSV-infected HeLa cells [20].
• There was a reciprocal relationship between the level of intracellular GSH, and that of the induction of heme oxygenase and p67 syntheses by delta 12-PGJ2 [15].

Analytical, diagnostic and therapeutic context of Dddd-PGD2

• The purified material was identified as delta 12-PGJ2 by gas chromatography/high resolution-selected ion monitoring using the molecular ion m/z 448[M]+. and ions [M - 15]+, [M - 43]+, [M - 100]+., and [M - 143]+ [19].
• Gel mobility shift assays demonstrated that delta 12-PGJ2 specifically stimulated the binding of two nuclear proteins to the E-box motif of this region [12].
• On agarose gel electrophoresis, DNA ladder formation was evident 24 h after the addition of delta 12-PGJ2 and remained apparent through 72 h, whereas G2/M accumulation was observed 6 h after the treatment [17].
• When the morphology of cells was examined by electron microscopy, L1210 cells incubated with a cytotoxic dose of PGA2 or delta 12-PGJ2 for 24 h showed the characteristic morphological features of apoptosis such as chromatin condensation, nuclear fragmentation and formation of apoptotic body [17].
• By Northern blotting, it was shown that delta 12-PGJ2 caused a marked reduction in the levels of the AFP mRNA and the albumin mRNA [10].

References