Polyamine synthesis and metabolism in normal and virus-infected protoplasts and chloroplasts

1. Intestinal epithelial cell proliferation was measured in rats maintained on total parenteral nutriton (TPN), in TPN rats given 300 μg of recombinant human epidermal growth factor (urogastrone-epidermal growth factor, URO-EGF) day−1 kg−1, and in further groups given URO-EGF and difluoromethylornithine (DFMO), an inhibitor of the enzyme ornithine decarboxylase (ODC). 2. URO-EGF significantly increased intestinal cell proliferation throughout the gastrointestinal tract. The proliferative response of the colon was particularly pronounced. 3. DFMO reduced the proliferative effect of urogastrone in the stomach and small intestine. DFMO also reduced URO-EGF-stimulated intestinal cell proliferation in the colon, but to a lesser extent. 4. It is concluded that ODC is essential for effecting the proliferative response of the stomach and small intestine to URO-EGF, but this role may be less important in the colon.

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Prevention of Metastasis by a Polyamine Synthesis Inhibitor in an Animal Bone Metastasis Model

Oncology ◽

10.1159/000012141 ◽

2000 ◽

Vol 59 (1) ◽

pp. 75-80 ◽

Cited By ~ 6

Author(s):

Hiroki Wakabayashi ◽

Hiroshige Hibasami ◽

Kohji Iida ◽

Norifumi Satoh ◽

Takashi Yamazaki ◽

...

Keyword(s):

Bone Metastasis ◽

Synthesis Inhibitor ◽

Polyamine Synthesis ◽

Animal Bone ◽

Metastasis Model

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Regulation of Polyamine Synthesis in Mammalian Cells

Progress in Polyamine Research - Advances in Experimental Medicine and Biology ◽

10.1007/978-1-4684-5637-0_24 ◽

1988 ◽

pp. 261-271 ◽

Cited By ~ 10

Author(s):

Lo Persson ◽

Ingvar Holm ◽

Louise Stjernborg ◽

Olle Heby

Keyword(s):

Mammalian Cells ◽

Polyamine Synthesis

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Dopaminergic regulation of polyamine synthesis in the rat pituitary gland

Molecular and Cellular Endocrinology ◽

10.1016/0303-7207(87)90031-1 ◽

1987 ◽

Vol 51 (3) ◽

pp. 219-225 ◽

Cited By ~ 7

Author(s):

L. Persson ◽

E. Rosengren

Keyword(s):

Pituitary Gland ◽

Polyamine Synthesis ◽

Rat Pituitary ◽

Dopaminergic Regulation

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Unusual aspects of the polyamine transport system affect the design of strategies for use of polyamine analogues in chemotherapy

Biochemical Society Transactions ◽

10.1042/bst0350318 ◽

2007 ◽

Vol 35 (2) ◽

pp. 318-321 ◽

Cited By ~ 9

Author(s):

J.L.A. Mitchell ◽

T.K. Thane ◽

J.M. Sequeira ◽

R. Thokala

Keyword(s):

Regulatory Protein ◽

Feedback System ◽

Uptake System ◽

Polyamine Synthesis ◽

Polyamine Analogues ◽

Binding Partners ◽

Polyamine Transport ◽

Polyamine Uptake ◽

Tumour Cell Growth

One strategy for inhibiting tumour cell growth is the use of polyamine mimetics to depress endogenous polyamine levels and, ideally, obstruct critical polyamine-requiring reactions. Such polyamine analogues make very unusual drugs, in that extremely high intracellular concentrations are required for growth inhibition or cytotoxicity. Cells exposed to even sub-micromolar concentrations of such analogues can achieve effective intracellular levels because these compounds are incorporated by the very aggressive polyamine uptake system. Once incorporated to these levels, many of these analogues induce the synthesis of a regulatory protein, antizyme, which inhibits both polyamine synthesis and the transporter they used to enter the cell. Thus this feedback system allows steady-state maintenance of effective cellular doses of such analogues. Accordingly, effective cellular levels of polyamine analogues are generally inversely related to their capacity to induce antizyme. Antizyme activity is down-regulated by interaction with several binding partners, most notably antizyme inhibitor, and at least a few tumour tissues exhibit deficiencies in antizyme expression. Our studies explore the role of antizyme induction by several polyamine analogues in their physiological response and the possibility that cell-to-cell differences in antizyme expression may contribute to variable sensitivities to these agents.

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Regulation of ornithine decarboxylase by hypoxia in pulmonary artery smooth muscle cells

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.1996.271.1.l31 ◽

1996 ◽

Vol 271 (1) ◽

pp. L31-L37 ◽

Cited By ~ 5

Author(s):

K. S. Harrod ◽

J. W. Olson ◽

M. N. Gillespie

Keyword(s):

Smooth Muscle ◽

Pulmonary Artery ◽

Smooth Muscle Cells ◽

Mrna Stability ◽

De Novo ◽

Hypoxic Exposure ◽

Polyamine Synthesis ◽

Mrna Content ◽

Pulmonary Artery Smooth Muscle ◽

Rate Limiting

The polyamines are a family of low-molecular-weight organic cations that play essential intracellular regulatory roles in cell growth and differentiation. Elevations in cellular polyamine contents necessary for most physiological and pathological events in the lung appear to be driven by increase de novo synthesis. In contrast, increases in lung cell polyamines required for hypoxic pulmonary vascular disease can be attributed to augmented transmembrane polyamine transport which may, in turn, be the result of hypoxia-related decreases in the activity of the initial and generally rate-limiting enzyme in de novo polyamine synthesis, ornithine decarboxylase (ODC). To begin to define the unusual mechanism whereby hypoxia governs polyamine regulatory pathways, the present study examined the impact of varying severity and durations of hypoxic exposure on ODC activity and mRNA content in cultured bovine main pulmonary artery smooth muscle cells (PASMC). The effect of hypoxia on the activity of another rate-limiting enzyme in polyamine synthesis, S-adenosylmethionine decarboxylase (AdoMet-DC), also was examined. Hypoxia caused time-dependent decreases in ODC and AdoMet-DC activities that were related to the severity of hypoxic exposure. Similarly, ODC mRNA content also was depressed by hypoxic exposure. The relationship between the decline in ODC activity and mRNA content was roughly linear. To determine whether hypoxia impairs ODC mRNA stability, two different inhibitors of transcription and Northern analyses were used to follow the decay in ODC mRNA abundance in hypoxic and normoxic PASMC. Densitometric scanning of Northern analysis indicated that ODC mRNA stability did not differ between hypoxic and normoxic PASMC. These results suggest that the reduction in ODC activity provoked by hypoxia in cultured bovine PASMC can be ascribed in part to a diminished transcriptional rate rather than to alterations in mRNA stability.

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