Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P00790 (PGA)
 2,475 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Prostaglandins of the A type (PGAs) function as signals for heat shock protein (hsp) synthesis in mammalian cells. In human K562 erythroleukemic cells, PGA1 induces the synthesis of a M(r) 70,000 hsp (hsp70) by cycloheximide-sensitive activation of heat shock transcription factor (HSF). Induction of hsp70 has been associated recently with the ability of PGA to protect K562 cells from thermal injury, establishing a thermotolerant state; however, the role of hsp70 in thermotolerance is still controversial. Because quercetin was shown to modulate hsp70 expression after heat shock in K562 cells, we have investigated the effect of this flavonoid on HSF activation, hsp70 synthesis, and thermotolerance in human K562 cells after induction with PGA1. Quercetin was found to inhibit hsp70 synthesis for a period of 3-6 h after PGA1 treatment. This transient block was exerted at the transcriptional level and was not due to the loss of HSF DNA-binding activity. After the initial delay, hsp70 synthesis reached the same rate as the PGA1-treated control, and it was actually prolonged in the presence of quercetin. In PGA1-treated cells, quercetin suppressed PGA1-induced thermotolerance completely if the heat shock was applied at a time (6 h) when hsp70 synthesis was inhibited, whereas it could not prevent the establishment of a thermotolerant state if the heat challenge was applied 24 h after treatment, when hsp70 synthesis was not affected. These results support strongly the hypothesis that hsp70 is involved in the establishment of thermotolerance in human cells.
 ...
PMID:Modulation of prostaglandin A1-induced thermotolerance by quercetin in human leukemic cells: role of heat shock protein 70. 854 66

Cellular stress can initiate prostaglandin (PG) biosynthesis which, through changes in gene expression, can modulate cellular functions, including cell growth. PGA(2), a metabolite of PGE(2), induces the expression of stress response genes, including gadd153 and hsp70, in HeLa cells and human diploid fibroblasts. PGs, gadd153, and hsp70 expression are also influenced by the cellular redox status. Polyphenolic glutathione conjugates retain the ability to redox cycle, with the concomitant generation of reactive oxygen species. One such conjugate, 2,3,5-tris(glutathion-S-yl)hydroquinone (TGHQ), is a potent nephrotoxic and nephrocarcinogenic metabolite of the nephrocarcinogen, hydroquinone. We therefore investigated the effects of TGHQ on PGE(2) synthesis and gene expression in a renal proximal tubular epithelial cell line (LLC-PK(1)). TGHQ (200 microM, 2 h) increases PGE(2) synthesis (2-3-fold) in LLC-PK(1) cells with only minor (5%) reductions in cell viability. This response is toxicant-specific, since another proximal tubular toxicant, S-(1, 2-dichlorovinyl)-L-cysteine (DCVC), stimulates PGE(2) synthesis only after massive (68%) reductions in cell viability. Consistent with the ability of TGHQ to generate an oxidative stress, both deferoxamine mesylate and catalase protect LLC-PK(1) cells from TGHQ-mediated cytotoxicity. Only catalase, however, completely blocks TGHQ-mediated PGE(2) synthesis, implying a major role for hydrogen peroxide in this response. TGHQ induces the early (60 min) expression of gadd153 and hsp70. However, while inhibition of cyclooxygenase with aspirin prevents TGHQ-induced PGE(2) synthesis, it does not affect TGHQ-mediated induction of gadd153 or hsp70 expression. In contrast, a stable PGE(2) analogue, 11-deoxy-16, 16-dimethyl-PGE(2) (DDM-PGE(2)), which protects LLC-PK(1) cells against TGHQ-mediated cytotoxicity, modestly elevates the levels of gadd153 and hsp70 expression. In addition, catalase and, to a lesser extent, deferoxamine mesylate block TGHQ-induced gene expression. Therefore, although TGHQ-induced generation of reactive oxygen species is required for PGE(2) synthesis and stress gene expression, acute TGHQ-mediated increases in gadd153 and hsp70 mRNA levels are independent of PGE(2) synthesis.
 ...
PMID:Stress- and growth-related gene expression are independent of chemical-induced prostaglandin E(2) synthesis in renal epithelial cells. 1068 35