scholarly journals Osmotic stress induces variation in cellular levels of ornithine decarboxylase-antizyme

1998 ◽  
Vol 329 (3) ◽  
pp. 453-459 ◽  
Author(s):  
L. A. John MITCHELL ◽  
G. Gary JUDD ◽  
Aviva LEYSER ◽  
Chung-youl CHOE
Keyword(s):  
Steady State ◽  
Ornithine Decarboxylase ◽  
Osmotic Shock ◽  
Regulatory Protein ◽  
Feedback Regulation ◽  
Integral Role ◽  
Htc Cells ◽  
Steady State Levels ◽  
The Common ◽  
Translational Start

The polyamines, and especially putrescine, play an integral role in the physiological response of cells to varying extracellular osmotic conditions. Ornithine decarboxylase (ODC) synthesis and stability, as well as the activity of the polyamine transporter, had all been reported to be very sensitive to media osmolarity in different cells and tissues, yet the mechanism of this complex, co-ordinated response was not known. In this study we have determined that all these aspects of osmotic-shock response may be mediated by the common regulatory protein, ODC-antizyme. HTC cells were induced for antizyme and then exposed to media of reduced osmotic strength. Both antizyme activity and protein decreased rapidly, under these conditions, to new steady-state levels that depended upon the degree of reduction in media tonicity. This antizyme reduction was found to be due to a rapid increase in antizyme degradation, with a half-life decrease from 75 min down to 45 min occurring immediately upon exchanging media. In complementary experiments, increased media tonicity induced elevated antizyme levels and stability. The sensitivity of antizyme turnover to osmotic conditions was also observed in DH23b cells, which contain elevated levels of more stable antizyme. Interestingly, the two main antizyme proteins, AZ-1 and AZ-2 (presumably products from the first and second translational start sites), differed in their responses to these changing osmotic conditions. Just as feedback regulation of antizyme synthesis provides an effective mechanism for maintaining stable polyamine levels, these studies suggest that alteration in the rate of antizyme degradation may be the mechanism whereby cells adjust steady-state polyamine levels in response to stimulation or stress.

Multiple mechanisms are responsible for altered expression of ornithine decarboxylase in overproducing variant cells

1986 ◽  
Vol 6 (8) ◽  
pp. 2865-2871
Author(s):  
L McConlogue ◽  
S L Dana ◽  
P Coffino
Keyword(s):  
Steady State ◽  
Gene Amplification ◽  
Ornithine Decarboxylase ◽  
Mrna Levels ◽  
Wild Type ◽  
Altered Expression ◽  
Cells Of Origin ◽  
Multistep Process ◽  
Steady State Levels ◽  
Synthesis And Degradation

We selected and characterized a series of mouse S49 cell variants that overproduce ornithine decarboxylase (ODC). Previously, we described variants that have an amplified ODC gene and produce about 500-fold more ODC than the wild-type cells of origin (L. McConlogue and P. Coffino, J. Biol. Chem. 258:12083-12086, 1983). We examined a series of independent variants that overproduce ODC to a lesser degree and found that a number of mechanisms other than gene amplification are responsible for the increased ODC activity. Variants were selected for resistance to 0.1 mM difluoromethylornithine, an inhibitor of ODC, by either a single or a multistep process. All showed increased ODC activity and increased ODC mRNA steady-state levels. The half-life of the enzyme was not increased in any of the variants. In one class of variant the increase of ODC mRNA was sufficient to account for ODC overproduction. In a second class, the rate of synthesis of ODC polypeptide per ODC mRNA was at least four- to eightfold higher than that in wild-type cells. Therefore, these variants were altered in the translatability of ODC mRNA. Southern analysis showed that gene amplification does not account for the increased ODC mRNA levels in any of the variants. In both variant and wild-type cells, ODC activity was responsive to changes in polyamine pools; activity was reduced following augmentation of pool size. This change in activity was associated with modification of the rate of synthesis and degradation of ODC but no change in the level of ODC mRNA.

scholarly journals Mammalian cell polyamine homeostasis is altered by the radioprotector WR1065

1998 ◽  
Vol 335 (2) ◽  
pp. 329-334 ◽  
Author(s):  
John L. A. MITCHELL ◽  
Jennifer RUPERT ◽  
Aviva LEYSER ◽  
Gary G. JUDD
Keyword(s):  
Ornithine Decarboxylase ◽  
Mammalian Cells ◽  
Regulatory Protein ◽  
Polyamine Metabolism ◽  
Intact Cells ◽  
Polyamine Synthesis ◽  
Radiation Induced ◽  
Htc Cells ◽  
Low Levels ◽  
The Stability

Mammalian cells become more susceptible to radiation-induced death and mutagenesis when restricted in their production of the natural polyamines putrescine, spermidine and spermine. The effects of polyamine deprivation are reversed by N-(2-mercaptoethyl)-1,3-diaminopropane (WR1065), a simple aminothiol that has been extensively studied for its radioprotectant properties. Because this compound and its oxidized derivative WR33278 bear some resemblance to the polyamines, it was hypothesized that radioprotection by WR1065 or its metabolites is derived, at least in part, from their ability to supplement the natural polyamines. To evaluate the ability of these aminothiol compounds to emulate polyamine function in intact cells, rat liver hepatoma (HTC) cells were treated with radioprotective doses of WR1065; the ability of this compound to affect various aspects of normal polyamine metabolism was monitored. Although cellular WR1065 was maintained at levels exceeding those of the polyamines, this aminothiol did not have any polyamine-like effect on the initial polyamine biosynthetic enzyme, ornithine decarboxylase, or on polyamine degradative reactions. On the contrary, treatment with relatively low levels of WR1065 resulted in an unexpected increase in putrescine and spermidine synthesis. WR1065 treatment enhanced the stability, and consequently the activity, of ornithine decarboxylase. This stabilization seems to result from a WR1065-induced delay in the synthesis of antizyme, a critical regulatory protein required in the feedback modulation of polyamine synthesis and transport. The increase in cellular spermidine induced by WR1065 might explain its antimutagenic properties, but is probably not a factor in protection against cell killing by radiation. This is the first evidence that compounds can be designed to control polyamine levels by targeting the activity of the regulatory protein antizyme.

scholarly journals Multiple mechanisms are responsible for altered expression of ornithine decarboxylase in overproducing variant cells.

1986 ◽  
Vol 6 (8) ◽  
pp. 2865-2871 ◽  
Author(s):  
L McConlogue ◽  
S L Dana ◽  
P Coffino
Keyword(s):  
Steady State ◽  
Gene Amplification ◽  
Ornithine Decarboxylase ◽  
Mrna Levels ◽  
Wild Type ◽  
Altered Expression ◽  
Cells Of Origin ◽  
Multistep Process ◽  
Steady State Levels ◽  
Synthesis And Degradation

We selected and characterized a series of mouse S49 cell variants that overproduce ornithine decarboxylase (ODC). Previously, we described variants that have an amplified ODC gene and produce about 500-fold more ODC than the wild-type cells of origin (L. McConlogue and P. Coffino, J. Biol. Chem. 258:12083-12086, 1983). We examined a series of independent variants that overproduce ODC to a lesser degree and found that a number of mechanisms other than gene amplification are responsible for the increased ODC activity. Variants were selected for resistance to 0.1 mM difluoromethylornithine, an inhibitor of ODC, by either a single or a multistep process. All showed increased ODC activity and increased ODC mRNA steady-state levels. The half-life of the enzyme was not increased in any of the variants. In one class of variant the increase of ODC mRNA was sufficient to account for ODC overproduction. In a second class, the rate of synthesis of ODC polypeptide per ODC mRNA was at least four- to eightfold higher than that in wild-type cells. Therefore, these variants were altered in the translatability of ODC mRNA. Southern analysis showed that gene amplification does not account for the increased ODC mRNA levels in any of the variants. In both variant and wild-type cells, ODC activity was responsive to changes in polyamine pools; activity was reduced following augmentation of pool size. This change in activity was associated with modification of the rate of synthesis and degradation of ODC but no change in the level of ODC mRNA.

scholarly journals Homeostatic Functions of Tecrem, a CD46-Like Regulatory Protein of Complement Activation, on Epithelial Cells in Carp Fish

2021 ◽  
Vol 9 (7) ◽  
pp. 687
Author(s):  
Harsha Prakash ◽  
Shiori Motobe ◽  
Takahiro Nagasawa ◽  
Tomonori Somamoto ◽  
Miki Nakao
Keyword(s):  
Epithelial Cells ◽  
Regulatory Protein ◽  
Physiological Role ◽  
Aqueous Environment ◽  
Microbial Invasion ◽  
Epithelial Cell Lines ◽  
Expression Behavior ◽  
The Common ◽  
Ginbuna Crucian Carp ◽  
Junction Proteins

Fish mucosal surface is a significant interface for pathogens to infect from an aqueous environment. In addition to mucosal innate and adaptive immune factors, epithelial cells are considered as a significant physical barrier against microbial invasion. Previously, we identified a mammalian CD46-like complement regulatory protein (Tecrem) in teleost and detected its expression on epithelial cells derived from fin, suggesting its physiological role on the fish surface. This study examines the homeostatic roles of Tecrem in maintaining the fish epithelium, by analyzing the expression behavior of Tecrem on the fin-derived epithelial cell lines (KF-1 from the common carp and CFS from ginbuna crucian carp) using monoclonal and polyclonal anti-Tecrem antibodies. Expression of KF-1 protein was associated with the adhesion of KF-1, and the adhesion was enhanced by anti-Tecrem treatments of the cells. Stimulation of the epithelial cells with anti-Tecrem enhanced wound healing, protein expression of tight-junction proteins, and cell density of the KF-1 and CFS monolayer culture. These results suggest that Tecrem on epithelial cells play a homeostatic role in maintaining intactness of the surface epithelial barrier, implying that modification of Tecrem expression may develop a novel tool to improve the first-line defense against pathogens in aquaculture.

scholarly journals The critical role of T cells in glucocorticoid-induced osteoporosis

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Lin Song ◽  
Lijuan Cao ◽  
Rui Liu ◽  
Hui Ma ◽  
Yanan Li ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Steady State ◽  
Side Effects ◽  
Critical Role ◽  
Wild Type ◽  
Receptor Activator ◽  
Steady State Levels ◽  
Induced Apoptosis

AbstractGlucocorticoids (GC) are widely used clinically, despite the presence of significant side effects, including glucocorticoid-induced osteoporosis (GIOP). While GC are believed to act directly on osteoblasts and osteoclasts to promote osteoporosis, the detailed underlying molecular mechanism of GC-induced osteoporosis is still not fully elucidated. Here, we show that lymphocytes play a pivotal role in regulating GC-induced osteoporosis. We show that GIOP could not be induced in SCID mice that lack T cells, but it could be re-established by adoptive transfer of splenic T cells from wild-type mice. As expected, T cells in the periphery are greatly reduced by GC; instead, they accumulate in the bone marrow where they are protected from GC-induced apoptosis. These bone marrow T cells in GC-treated mice express high steady-state levels of NF-κB receptor activator ligand (RANKL), which promotes the formation and maturation of osteoclasts and induces osteoporosis. Taken together, these findings reveal a critical role for T cells in GIOP.

The Olympic Games as a News Shock

2017 ◽  
Vol 19 (6) ◽  
pp. 884-906 ◽  
Author(s):  
Viktoria C. E. Langer ◽  
Wolfgang Maennig ◽  
Felix Richter
Keyword(s):  
Steady State ◽  
Olympic Games ◽  
Structural Models ◽  
Adjustment Process ◽  
Dynamic Adjustment ◽  
Economic Variables ◽  
Long Run ◽  
News Shock ◽  
Steady State Levels ◽  
The Olympic Games

The awarding of the Olympic Games to a certain city or the announcement of a city’s Olympic bid may be considered as a news shock that affects agents’ market expectations. A news shock implies potential impacts on the dynamic adjustment process that change not only the volatility but also the long-run steady-state levels of endogenous economic variables. In this study, we contribute to and extend previous researchers’ attempts to empirically test for the Olympic Games as a news shock by implementing full structural models and by matching Olympic hosts and bidders to structurally similar countries.

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