Regulation of ornithine decarboxylase mRNA by phorbol esters and insulin in normal and C‐kinase‐deficient rat hepatoma cells

Butler, Andrew C.; Cohn, William B.; Mar, Penny K.; Montgomery, Raechelle L.

doi:10.1002/jcp.1041470210

Cited by 17 publications

(12 citation statements)

References 50 publications

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“…The mRNAs of keratin 18 (Krt1-18) and, in line with earlier reports [35][36][37][38], ornithin decarboxylase (Odc1) and actin (Acta1) were downregulated by hyperosmolarity but upregulated by insulin (Table 2B, no. 68, 53 and 47).…”

Section: Osmoregulated Genessupporting

confidence: 77%

Modulation of Gene Expression Profiles by Hyperosmolarity and Insulin

Schäfer

Gehrmann

Richter

et al. 2007

Cell Physiol Biochem

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Cell hydration changes play a key role in the regulation of cell function and critically affect insulin sensitivity of carbohydrate- and protein metabolism. Here, the modulation of gene expression profiles by hyperosmolarity and insulin was examined in H4IIE rat hepatoma cells by cDNA/oligonucleotiode array-, Northern- and Western blot analysis. Osmosensitive expression of the insulin-like growth factor binding protein Igfbp1, the multidrug resistance protein Mrp5 (Abcc5a) and cyclin D1 (Ccnd1) was established at the mRNA and protein level. Despite a hyperosmotic increase of cyclin D1 mRNA induction by insulin, the cyclin D1 protein expression was decreased by hyperosmolarity, suggesting a hyperosmotic interference with cyclin D1 mRNA translation. Hyperosmolarity at the mRNA level blunted the insulin response of betaine homocysteine-S-methyl transferase, the multidrug resistance proteins Mdr1a (Abcb1a) and 2 (Abcb4), the Igfbp 2 and 5, cyclin G1, dual specificity phosphatase Dusp1, signal transducers and activators of transcription Stat3 and 5, catalase and the bile salt export pump Bsep (Abcb11), whereas the insulin response was increased for Mrp5, cyclin D1 and the phosphoenolpyruvate carboxykinase. Insulin effects on the mRNA expression of the eukaryotic initiation factor 4E binding protein 4e-bp1, tubulin, gene 33, growth hormone receptor, keratin18, ornithine decarboxylase and heme oxygenase 1 were largely insensitive to hyperosmolarity. The data indicate that hyperosmolarity differentially modulates insulin sensitivity at the level of gene expression.

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Section: Osmoregulated Genessupporting

confidence: 77%

Modulation of Gene Expression Profiles by Hyperosmolarity and Insulin

Schäfer

Gehrmann

Richter

et al. 2007

Cell Physiol Biochem

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“…In addition, previous studies suggested that ODC could represent a downstream element of PKC-mediated mitogenic signalling [29][30][31], and might be involved in tumour cell invasion in vitro [32][33][34][35]. These data raised the possibility that ODC also played a role in the abovementioned actions of PKC on the invasiveness of the glioma cell lines.…”

Section: Involvement Of Odc In Pkc-mediated Mt1-mmp Expression Mmp-2mentioning

confidence: 69%

“…Available in vitro data suggest an involvement of mitogen-activated protein kinase/extracellular-signal-regulated kinase 1 (MEK-1) and ODC in the stimulatory effects of PKC on tumour cell proliferation [29][30][31], while ODC and extracellular-signal-regulated kinases 1 and/or 2 (ERK1/2) have been implicated in tumour cell invasion [32][33][34][35][36][37][38]. Therefore, we also asked whether these enzyme systems were involved in the actions of PKC on the invasiveness of the glioma cell lines.…”

Section: Introductionmentioning

confidence: 99%

Protein Kinase C-Mediated in vitro Invasion of Human Glioma Cells through Extracellular-Signal-Regulated Kinase and Ornithine Decarboxylase

et al. 2000

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We investigated the involvement of protein kinase C (PKC) in the in vitro invasiveness of the A-172, U-87 and U-373 human glioma cell lines, as well as the role of ornithine decarboxylase (ODC) and/or extracellular-signal-regulated kinase (ERK) in the actions of PKC. Thus, cells were treated under serum-free conditions with the PKC activator phorbol 12-myristate 13-acetate (PMA), or with the PKC inhibitors bisindolylmaleimide I (GF 109203X) or calphostin C in the absence or presence of the ODC inhibitor D,L-α-difluoromethylornithine (DFMO), and/or the mitogen-activated protein kinase/extracellular-signal-regulated kinase inhibitor 2′-amino-3′-methoxyflavone (PD 098059). Subsequently, cells were assessed for membrane-type 1 matrix metalloproteinase (MT1-MMP) mRNA contents, 72-kD latent, and 59/62-kD activated matrix metalloproteinase 2 (MMP-2) in conditioned media, as well as invasiveness. For these purposes, we used Northern blot analysis, gelatine zymography, and an in vitro filter invasion assay, respectively. Data were related to those found with untreated cells. PKC activity was 2- to 3-fold stimulated by PMA (100 nM for 30 min), and about 2-fold inhibited by calphostin C (40 nM for 2 h) or GF 109203X (5 µM for 20 min). This was accompanied by a similar increase or decrease, respectively, in MT1-MMP mRNA expression, 59/62-kD MMP-2 activity, and in vitro invasion. Inhibition of ODC activity (about 2-fold by 24 h DFMO 5 mM), ERK activation (almost completely by 20 min PD 098059 50 µM), or both these enzymes simultaneously led to a reduction by about half in levels of MT1-MMP mRNA, 59/62-kD MMP-2 activity, and invasion in untreated as well as PMA-stimulated cells. The use of these compounds did not significantly alter the inhibitory effects of GF 109203X or calphostin C. Modulation of PKC and/or ERK activity resulted in corresponding changes in ERK and/or ODC activities, but interference with ODC affected neither ERK nor PKC. Our data suggest a regulatory role for PKC, in co-operation with ERK and ODC, in glioma cell invasion, by modulation of MT1-MMP mRNA expression and MMP-2 activation.

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“…HindIII fragment (16) Pups of three or four pregnant rats in each group were used for each datum point. We measured tissue ODC activity in five pups per litter and calculated the mean value.…”

mentioning

confidence: 99%

Acute hypoxia increases ornithine decarboxylase activity and polyamine concentrations in fetal rat brain.

Longo

Packianathan

McQueary

et al. 1993

Proc. Natl. Acad. Sci. U.S.A.

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The cellular responses to hYpoxia are poorly understood. To test the hypothesis that ornithine decarboxylase (ODC; L-ornithine carboxy-lyase; EC 4.1.1.17) activity and polyamine concentrations change in response to acute hypoxia we performed the following studies. Pregnant Sprague-Dawley rats inspired various 02 concentrations (9-21%) for various time periods (0.5-48 h) from days 15 to 21 of gestation. In fetal brains we measured the activity of ODC, ODC mRNA, and polyamines. In response to 4-h acute mild hypoxia, ODC activity in fetal rat brain (cerebrum, cerebellum and hippocampus) increased to 330-450% from control values (P < 0.001), after which it declined to control levels in 6-8 h. The 4-h ODC response varied inversely with inspired 02 concentration and was not mimicked by P2 agonist or blocked by 2-antagonist administration. The ODC response was associated with an increase in fetal brain putrescine concentration to 190% above control at 4-6 h (P < 0.01) and an increase in the polyamines spermidine and spermine to about 115% above control at 6-8 h. We also observed that ODC mRNA increased sigificantly after 2-4 h of hypoxia. ODC activity and polyamine concentrations appear to be useful enzymatic markers for fetal brain hypoxia. The magnitude and time course of the acute hypoxic ODC increase were similar to responses to extracellular signals that result in differentiation or cell growth. Thus, the well-defined and regulated ODC activity response may represent a protective mechanism in brain to hypoxia. The brain is known to be particularly vulnerable to oxygen deprivation. Recently, considerable interest has centered on the role of ischemia (lack of blood flow) on brain neurochemistry (1, 2), but relatively little recent work has focused on the neurochemical effects of hypoxia (relative 02 lack) per se (3, 4). In addition, there are few well-documented biochemical or cellular markers of hypoxic effects in brain or other tissues.In this report we present the hypothesis that ornithine decarboxylase (ODC; L-ornithine carboxy-lyase; EC 4.1.1.17) activity could be an enzymatic marker responsive to hypoxia in fetal rat brain. ODC activity is tightly regulated in growing tissue (5) and is sensitive to extracellular signals (6). ODC is the rate-limiting enzyme in polyamine biosynthesis, is highly inducible, has a short half-life (about 20 min), and is absolutely required for cell growth and proliferation (7-9). Thus, ODC activity is an excellent marker for changes in polyamine metabolism, which plays key roles in DNA, RNA, and protein synthesis. Our rationale was that if mild hypoxia affected any of these processes, then ODC activity and polyamine concentrations could be sensitive markers for these changes. Furthermore, because ODC activity is relatively high in growing fetal tissue (10, 11) we expected to be able to detect altered ODC activity in response to hypoxia.We specifically chose maternal hypoxic exposures (9-16% inspired 02), which might be experienced during fetal development, and not ischemic e...

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Regulation of ornithine decarboxylase mRNA by phorbol esters and insulin in normal and C‐kinase‐deficient rat hepatoma cells

Cited by 17 publications

References 50 publications

Modulation of Gene Expression Profiles by Hyperosmolarity and Insulin

Modulation of Gene Expression Profiles by Hyperosmolarity and Insulin

Protein Kinase C-Mediated in vitro Invasion of Human Glioma Cells through Extracellular-Signal-Regulated Kinase and Ornithine Decarboxylase

Acute hypoxia increases ornithine decarboxylase activity and polyamine concentrations in fetal rat brain.

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