Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.6 (RNA polymerase)
 34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To elucidate the molecular basis of the induction of peroxisomal enzymes, transcriptional regulation of the acyl-CoA oxidase (AOX) gene by dehydroepiandrosterone sulfate (DHEAS) was examined using primary cultures of rat hepatocytes. Incubation of the hepatocytes with 0.1 mM DHEAS resulted in a progressive increase in the cellular AOX mRNA level, which after 24 h reached a 5.6-fold higher level than that in the control cells treated with vehicle alone. However, this mRNA induction was completely inhibited by alpha-amanitin, an RNA polymerase II inhibitor. When examined by the nuclear run-on transcription assay, the rate of de novo synthesis of AOX mRNA was 3- to 4-fold higher in the hepatocytes exposed to DHEAS than in the control cells, even after 3h. These results indicate that DHEAS acts directly on hepatocytes to activate the transcription of the AOX gene, which leads to the marked induction of AOX in the cell.
 ...
PMID:Transcriptional induction of Acyl-CoA oxidase by dehydroepiandrosterone sulfate in cultured rat hepatocytes. 913 72

Peroxisome proliferators (PP) are known hepatocarcinogens in rats and mice. We have investigated the ability of Wyeth-14 643 (Wy), a PP and potent rodent carcinogen, to induce replicative DNA synthesis and to modulate the levels of peroxisome proliferator activated receptor-alpha (PPAR alpha) transcriptionally-dependent genes in primary rat hepatocyte (HPC) cultures and hepatocyte/nonparenchymal cell (HPC/NPC) co-cultures maintained on Matrigel. Four days after plating, cells were treated with Wy and replicative DNA synthesis was quantitated using [3H]thymidine incorporation and specific mRNA transcript levels were determined by reverse-transcriptase polymerase chain reaction (RT-PCR). An increase in HPC replicative DNA synthesis was detected at 48 h in both Wy-treated HPC and HPC/NPC co-cultures relative to controls. This increase was approximately 3- and 6-fold in HPC and HPC/NPC cultures respectively, and was Wy concentration-dependent. The levels of PPAR alpha-transcriptionally dependent genes [cytochrome P4504A1, acyl-CoA oxidase (AOxase), and liver-fatty acid binding protein (L-FABP)] transcripts were determined as indicators of PPAR alpha activation. These transcripts increased dose-dependently at 48 h in HPC/NPC cultures up to 10 microM Wy. Similarly, RT-PCR product levels were also increased in HPC cultures with 10 microM Wy at 48 h. In conclusion, we have investigated the transcription of PPAR alpha-dependent genes and HPC replicative DNA synthesis by Wy in HPC/NPC co-cultures. Results of this work are clearly more reflective of the known in vivo effects of PP and suggest that HPC/NPC co-cultures are more appropriate than HPC cultures for such studies. The effect of PP on human HPC/NPC co-cultures is currently being investigated in our laboratory in an attempt to assess human risks to these chemicals more directly.
 ...
PMID:Induction of replicative DNA synthesis and PPAR alpha-dependent gene transcription by Wy-14 643 in primary rat hepatocyte and non-parenchymal cell co-cultures. 939 5

The adipocyte-derived cytokine, resistin, has been proposed as the link between obesity and type 2 diabetes mellitus in murine models. In humans, resistin is identical to FIZZ3 (found in inflammatory zone 3), which belongs to a family of proteins that appears to be involved in inflammatory processes. To study the mechanisms by which fibrates improve glucose homeostasis, we determined resistin mRNA levels by using relative quantitative reverse-transcriptase-polymerase chain reaction (RT-PCR) in omental white adipose tissue samples obtained from patients treated with placebo or fenofibrate (200 mg/d) for 8 weeks before elective cholecystectomy. Fenofibrate treatment reduced total plasma cholesterol and low-density lipoprotein (LDL)-cholesterol levels by 24% and 35%, respectively. Compared with placebo values, a 2.4-fold induction in resistin mRNA levels was observed in white adipose tissue of fenofibrate-treated patients, whereas no changes were observed in the mRNA levels of the well-known perosixome proliferator-activated receptor (PPAR) target genes CD36, acyl-CoA oxidase, and carnitine palmitoyltransferase. These findings indicate that resistin changes were not related to PPAR activation by fenofibrate. Interestingly, resistin mRNA levels showed a negative correlation with plasma cholesterol levels (r2 =.53, P =.039, n = 8), but not with triglyceride levels (r2 =.02, P =.73, n = 8). These results suggest that cholesterol regulates resistin expression in human white adipose tissue.
 ...
PMID:Reductions in plasma cholesterol levels after fenofibrate treatment are negatively correlated with resistin expression in human adipose tissue. 1264 75