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

Glutathione (GSH) synthesis is differentially regulated in the embryo and visceral yolk sac (VYS) of the developing rat conceptus. The innate capacity to respond to environmental insult and chemical exposure by inducing de novo GSH synthesis may help to determine overall cell sensitivity and/or resistance to chemically induced malformation. Specific activities of glutamate-cysteine ligase (GCL), the rate limiting enzyme in GSH synthesis, were determined by measuring the formation of gamma-glutamylcysteine (GC) in homogenates prepared from rat embryos and VYSs. GC formation increased linearly with time and with relative protein concentration. Specific activities were found to be 60.5 +/- 3.2 and 118.9 +/- 4.2 pmol GC/mg protein/min in the gestational day (GD) 10 embryo and VYS, respectively, and 22.7 +/- 0.4 and 71.3 +/- 0.6 pmoles GC/mg protein/min in the respective GD 11 embryo and VYS. Apparent kinetic constants determined from embryo and VYS homogenates gave respective apparent K(m) values for glutamate of 0.75 and 1.38 mM and for cysteine 0.03 mM in both tissues. Apparent V(max) values were higher in the VYS in each case, corresponding with a lower apparent K(m) and higher GCL activity. GCL specific activities increased significantly following a 24 h in vitro exposure to diethyl maleate (DEM) and diamide, but remained unchanged following exposure to prostaglandin A(2) (PGA(2)) and t-butylated hydroxytoluene (BHT). Basal expression of GCL catalytic subunit (GCL(C)) and regulatory subunit (GCL(R)) was 59- and 25-fold higher in VYS, respectively, compared to the embryo. Quantitative real-time fluorescence reverse transcriptase polymerase chain reaction (RT-PCR) showed that following DEM and diamide treatment, GCL(C) expression increased up to 19-fold in embryonic tissues but was not induced in the VYS. Only DEM increased the expression of the light/regulatory subunit GCL(R) in the embryo (8-fold). Densitometry of immunoblots revealed approximately 75% more GCL(C) in the VYS than in the embryo. Following treatments, a marked increase was induced in embryonic GCL(C) content with both DEM (85%) and diamide (19%), but in the VYS, only DEM caused an increase in GCL(C) protein (38%).
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PMID:Spatial activities and induction of glutamate-cysteine ligase (GCL) in the postimplantation rat embryo and visceral yolk sac. 1511 89

The biological function as well as gene expression of the MRP/GS-X pump is closely linked with cellular GSH metabolism. This article describes two important aspects, i.e., 1) a role of the MRP/GS-X pump in the modulation of cell cycle arrest induced by anticancer prostaglandins; 2) coordinated up-regulation of gamma-glutamylcysteine synthetase gamma-GCS) and MRP1 genes. The A and J series of prostaglandins (PGs) accumulate in the nuclei to suppress the proliferation of cancer cells. Delta(7)-Prostaglandin A(1) (Delta(7)-PGA(1)) methyl ester, a synthetic anticancer PG, increased the mRNA level of the cyclin-dependent kinase inhibitor p21(Sdi1/CIP1/WAF1) in human leukemia HL-60 cells. The induction of p21(Sdi1/CIP1/WAF1) was associated with the accumulation of hypophosphorylated retinoblastoma protein (pRB) and the suppression of c-myc gene expression. Unlike HL-60 cells, cisplatin-resistant HL-60/R-CP cells were insensitive to Delta(7)-PGA(1) methyl ester. While c-myc expression was transiently suppressed, neither G1 arrest nor hypophosphorylation of pRB was observed with the anticancer PG. Plasma membrane vesicles from HL-60/R-CP cells showed an enhanced level of GS-X pump activity toward the glutathione S-conjugate of Delta(7)-PGA(1) methyl ester. GIF-0019, a potent inhibitor of the GS-X pump, dose-dependently enhanced the cellular sensitivity of HL-60/R-CP cells to Delta(7)-PGA(1) methyl ester, resulting in G1 arrest. The GS-X pump is suggested to play a pivotal role in modulating the biological action of the anticancer PG. The expression of MRP1 and gamma-GCS genes can be coordinately up-regulated by cisplatin, 1-[5-(4-amino-2-methyl)pyrimidyl]methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU), and heavy metals in human cancer cells. For the up-regulation of these genes, both transcriptional and posttranscriptional regulations are considered to be involved.
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PMID:A new aspect on glutathione-associated biological function of MRP/GS-X pump and its gene expression. 1900 85