Glucocorticoid induced expression of glutamine synthetase in hepatoma cells

Gaunitz, Frank; Heise, Kerstin; Schumann, Robert; Gebhardt, Rolf

doi:10.1016/s0006-291x(02)02044-2

Cited by 20 publications

(20 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In rat hepatoma cells, GS mRNA is elevated in the presence of glucocorticoids (Gaunitz et al, 2002). Furthermore, a glucocorticoid responsive element (GRE) was identified in the first intron of the rat GS gene (Gaunitz et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Effects of crowding on ornithine–urea cycle enzyme mRNA expression and activity in gulf toadfish (Opsanus beta)

Laberge

Walsh

McDonald

2009

Journal of Experimental Biology

View full text Add to dashboard Cite

SUMMARYThe gulf toadfish (Opsanus beta) is a facultatively ureotelic fish that excretes primarily urea under conditions of crowding or confinement. To examine the relationship between ammonia production, urea production and the ornithine-urea cycle (O-UC) enzyme activity and mRNA expression, we subjected toadfish to two-day and seven-day crowding regimes. Plasma cortisol levels were measured and liver tissue was assayed for ammonia and urea concentrations. Liver glutamine synthetase (GS), carbamoyl phosphate synthetase III (CPS), ornithine carbamoyl transferase (OCT) and arginase (ARG) activities were also measured. Quantitative PCR was utilized to determine liver GS, CPS, OCT, ARG, argininosuccinate synthetase (ASS) and argininosuccinate lyase (ASL) mRNA expression. Hepatic ammonia concentrations decreased with increased duration of crowding whereas liver urea and circulating cortisol levels increased. An elevation in enzyme activity with increased duration of crowding was observed for all four O-UC enzymes examined. By contrast, mRNA expression was variable for the O-UC enzymes and only CPS and ASS had mRNA expression levels that were elevated in crowded fish. These results suggest that the activities of O-UC enzymes are better predictors for urea production than O-UC enzyme mRNA expression levels.

show abstract

Section: Discussionmentioning

confidence: 99%

Effects of crowding on ornithine–urea cycle enzyme mRNA expression and activity in gulf toadfish (Opsanus beta)

Laberge

Walsh

McDonald

2009

Journal of Experimental Biology

View full text Add to dashboard Cite

show abstract

“…In addition, there is evidence of post-translational regulation in fao hepatoma cells [23]. Working with rats in vivo Abcouwer et al [16] showed that glucocorticoid treatment increased glutamine synthetase mRNA abundance in skeletal muscle, lung, heart and possibly liver, but not in thymus.…”

Section: Discussionmentioning

confidence: 99%

“…Extensive study has shown that the hormonal regulation of glutamine synthetase expression is mainly at the level of gene transcription [3,6,9,23].…”

mentioning

confidence: 99%

Glutamine, insulin and glucocorticoids regulate glutamine synthetase expression in C2C12 myotubes, Hep G2 hepatoma cells and 3T3 L1 adipocytes

Wang¹,

Watford²

2007

Biochimica et Biophysica Acta (BBA) - General Subjects

View full text Add to dashboard Cite

SummaryThe cell-specific regulation of glutamine synthetase expression was studied in three cell lines. In C2C12 myotubes, glucocorticoids increased the abundance of both glutamine synthetase protein and mRNA. Culture in the absence of glutamine also resulted in very high glutamine synthetase protein abundance but mRNA levels were unchanged. Glucocorticoids also increased the abundance of glutamine synthetase mRNA in Hep G2 hepatoma cells but this was not reflected in changes in protein abundance. Culture of Hep G2 cells without glutamine resulted in very high levels of protein, again with no change in mRNA abundance. Insulin was without effect in both C2C12 and Hep G2 cells. In 3T3 L1 adipocytes glucocorticoids increased the abundance of both glutamine synthetase mRNA and protein, insulin added alone had no effect but in the presence of glucocorticoids resulted in lower mRNA levels than seen with glucocorticoids alone, although protein levels remained high under such conditions. In contrast to the other cell lines glutamine synthetase protein levels were relatively unchanged by culture in the absence of glutamine. The results support the hypothesis that in myocytes, and hepatomas, but not in adipocytes, glutamine acts to moderate glutamine synthetase induction by glucocorticoids. Keywords glutamine; glutamine synthetase; skeletal muscle; liver; adipocyte; insulin; glucocorticoids Glutamine is the most abundant free α amino acid in most mammalian species. The plasma glutamine pool is turning over very rapidly since it plays important roles in the interorgan transport of carbon, nitrogen and energy [1]. Although present in the diet, most ingested glutamine is metabolized by the small intestinal mucosa and thus the large body pool of glutamine is synthesized de novo [2]. The only enzyme capable of glutamine synthesis is glutamine synthetase (L-glutamate:ammonia ligase (ADP) EC 6.3.1.2) which is found in relatively high activity in skeletal muscle, adipose tissue, liver, lungs, brain and small intestine, but its regulation is poorly understood [3][4][5][6][7][8][9]. The enzyme is not known to be subject to regulation by allosteric or covalent modification mechanisms and those agents that show stimulatory or inhibitory actions in vitro are unlikely to play any physiological role [5,7]. The enzyme is however, subject to long-term regulation via changes in the amount of enzyme protein. Diabetes increases expression of the enzyme in skeletal muscle and adipose tissue and

show abstract

“…Although an increasing number of genes, including the target of GR, were reported to have intronic regulatory elements, the regulatory mechanism is not clear (Kastan et al 1992;Oda et al 2000;de Stanchina et al 2004;Gaunitz et al 2002). In our study, considering the various potential of the intronic GRE and/or other GREs positioned at distant loci, we investigated transcripts derived from the GZMA gene and for the first time discovered an alternative transcript which starts from 290 bp downstream of GRE.…”

Section: Discussionmentioning

confidence: 96%

“…More recently, U et al (2004) investigated the genomic organization of GZMA and identified the consensus GRE in the first intronic region of GZMA gene, speculating the induction potential of intronic GRE to be multiple functions in the context of the complex genomic organization. However, many studies only speculated upon the induction potential of the putative intronic GRE, and lack evidence on the GRE working as an enhancer (U et al 2004;Kastan et al 1992;Oda et al 2000;de Stanchina et al 2004;Gaunitz et al 2002). Hence, whether glucocorticoid can induce GZMA via the intronic GRE or not should be more critically assessed.…”

Section: Introductionmentioning

confidence: 99%

Glucocorticoid-induced alternative promoter usage for a novel 5′ variant of granzyme A

et al. 2006

View full text Add to dashboard Cite

Glucocorticoids exert diverse physiological functions through transcriptional regulation of genes including granzyme A (GZMA). GZMA is one of the apoptotic effectors localized in cytotoxic T lymphocytes and is considered to mediate glucocorticoidinduced apoptosis of human leukemia 697 cells. In the present study, we identified a novel 5¢ variant transcript of GZMA in dexamethasone (DEX)-treated 697 cells. We designated this novel transcript as GZMAb. The transcription of GZMAb starts at 290 bp downstream of the first intronic glucocorticoid response element (GRE). Chromatin immunoprecipitation assay showed that glucocorticoid receptor (GR) binds to the intronic GRE in a DEX-dependent manner. Luciferase assay and RT-PCR also showed that DEX induces GZMAb transcription mediated by GR binding to the intronic GRE. Our results show that there exist at least two transcripts in human GZMA, whose expression is differentially regulated by glucocorticoid.

show abstract

Glucocorticoid induced expression of glutamine synthetase in hepatoma cells

Cited by 20 publications

References 28 publications

Effects of crowding on ornithine–urea cycle enzyme mRNA expression and activity in gulf toadfish (Opsanus beta)

Effects of crowding on ornithine–urea cycle enzyme mRNA expression and activity in gulf toadfish (Opsanus beta)

Glutamine, insulin and glucocorticoids regulate glutamine synthetase expression in C2C12 myotubes, Hep G2 hepatoma cells and 3T3 L1 adipocytes

Glucocorticoid-induced alternative promoter usage for a novel 5′ variant of granzyme A

Contact Info

Product

Resources

About