Polyamine transport in mammalian cells. An update

Seiler, Nikolaus; Delcros, Jean‐Guy; Moulinoux, Jacques-Philippe

doi:10.1016/1357-2725(96)00021-0

Cited by 333 publications

(340 citation statements)

References 121 publications

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“…They had been released because the affinity of the polyamines for the GlcNH 3 ϩ -enriched HS of Gpc-1 had been diminished. In keeping with these results, DFMO treatment is known to increase both the V max and K m for polyamine binding to the putative transporter, which means increased capacity for polyamine uptake, but reduced overall affinity (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11).…”

Section: Involvement Of Gpc-1 In Sperminementioning

confidence: 57%

“…An excess of intracellular polyamines induces expression of antizyme, which forms a complex with ornithine decarboxylase, leading to rapid degradation of ornithine decarboxylase, thereby constituting a negative feedback loop. A decrease in the polyamine content of cells leads to a marked increase in the rate of polyamine uptake from the environment (1)(2)(3)(4)(5)(6)(7)(8)34). Antizyme is also involved in polyamine transport by inhibiting uptake and by stimulating excretion (34).…”

Section: Discussionmentioning

confidence: 99%

“…Cells (even uptake-deficient cells) can also secrete polyamines (for reviews, see Refs. [1][2][3][4][5][6][7][8]. Polyamine transport proteins and their genes have been identified in prokaryotes (9).…”

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confidence: 99%

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Glypican-1 Is a Vehicle for Polyamine Uptake in Mammalian Cells

Belting

Mani

Jönsson

et al. 2003

Journal of Biological Chemistry

151

113

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Polyamines (putrescine, spermidine, and spermine) are essential for growth and survival of all cells. When polyamine biosynthesis is inhibited, there is up-regulation of import. The mammalian polyamine transport system is unknown. We have previously shown that the heparan sulfate (HS) side chains of recycling glypican-1 (Gpc-1) can sequester spermine, that intracellular polyamine depletion increases the number of NO-sensitive N-unsubstituted glucosamines in HS, and that NO-dependent cleavage of HS at these sites is required for spermine uptake. The NO is derived from S-nitroso groups in the Gpc-1 protein. Using RNA interference technology as well as biochemical and microscopic techniques applied to both normal and uptake-deficient cells, we demonstrate that inhibition of Gpc-1 expression abrogates spermine uptake and intracellular delivery. In unperturbed cells, spermine and recycling Gpc-1 carrying HS chains rich in Nunsubstituted glucosamines were co-localized. By exposing cells to ascorbate, we induced release of NO from the S-nitroso groups, resulting in HS degradation and unloading of the sequestered polyamines as well as nuclear targeting of the deglycanated Gpc-1 protein. Polyamine uptake-deficient cells appear to have a defect in the NO release mechanism. We have managed to restore spermine uptake partially in these cells by providing spermine NONOate and ascorbate. The former bound to the HS chains of recycling Gpc-1 and S-nitrosylated the core protein. Ascorbate released NO, which degraded HS and liberated the bound spermine. Recycling HS proteoglycans of the glypican-type may be plasma membrane carriers for cargo taken up by caveolar endocytosis.

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Section: Involvement Of Gpc-1 In Sperminementioning

confidence: 57%

Section: Discussionmentioning

confidence: 99%

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Glypican-1 Is a Vehicle for Polyamine Uptake in Mammalian Cells

Belting

Mani

Jönsson

et al. 2003

Journal of Biological Chemistry

151

113

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“…26 As discussed above, none of the PAHA analogues tested were taken up by the polyamine transport system. However, PABA 21 was shown to be an effective noncompetitive inhibitor of the uptake of 14 C-spermidine, suggesting that it is a substrate for the polyamine transport system.…”

Section: Discussionmentioning

confidence: 95%

Polyaminohydroxamic Acids and Polyaminobenzamides as Isoform Selective Histone Deacetylase Inhibitors

et al. 2008

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A series of polyaminohydroxamic acids (PAHAs) and polyaminobenzamides (PABAs) were synthesized and evaluated as isoform-selective histone deacetylase (HDAC) inhibitors. These analogues contain a polyamine chain to increase affinity for chromatin and facilitate cellular import. Seven PAHAs inhibited HDAC >50% (1 µM), and two PABAs inhibited HDAC >50% (5 µM). Compound 17 increased acetylated α-tubulin in HCT116 colon tumor cells 253-fold but only modestly increased p21 waf1 and acetylated histones 3 and 4, suggesting that 17 selectively inhibits HDAC 6. PABA 22 alone minimally increased p21 waf1 and acetylated histones 3 and 4 but caused dose-dependent increases in p21 waf1 in combination with 0.1 µM 5-azadeoxycytidine. Finally, 22 appeared to be a substrate for the polyamine transport system. None of these compounds were cytotoxic at 100 µM. PAHAs and PABAs exhibit strikingly different cellular effects from SAHA and have the potential for use in combination antitumor therapies with reduced toxicity.

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“…Virtually all cells, including intestinal mucosa cells, can take up and secrete PAs, most of them by carrier-mediated mechanisms (for review, see Seiler et al 1996). Considering the case of digestive tissues, it seems that the requirement for PAs during growth and differentiation is fulfilled by their cellular uptake from external sources rather than by a de novo synthesis.…”

Section: Discussionmentioning

confidence: 99%

Pancreatic Exocrine Secretions as a Source of Luminal Polyamines in Pigs

Loret

Brolet

Pierzynowski

et al. 2000

Experimental Physiology

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The goal of the present study was twofold: (1) to detect the possible storage of dietary polyamines (PAs) in various tissues and (2) to investigate the role of dietary PAs in the differentiation of the pig intestinal epithelium. A first experimental series was designed to assess the accumulation of either milk PAs (mostly spermidine) or orally administered spermine (SPM) in piglet red blood cells (RBCs) and plasma, a preliminary stage in their distribution to growing and storage organs. Though PA concentrations of piglet RBCs and plasma were generally significantly higher than their sow counterparts, our experimental conditions failed to demonstrate that this increase could stem from ingested PAs. A second experimental series dealt with the determination of disaccharidase specific activities in proximal and distal parts of piglet gut on the 26th and 29th days after birth (preweaning time). In agreement with observations made previously on rat pups, we observed an increase in maltase specific activity (SA) at the end of the suckling period (the observed increase in sucrase SA was not significant). However, orally administered SPM did not affect this activity. Compared to the constant protein concentrations observed in both parts of the gut, the pancreatic protein content decreased sharply between the 26th and 29th postnatal days. At the same time pancreatic concentrations of spermidine (SPD) also decreased, suggesting that some pancreatic PAs were released as the organ secreted its proteins. In accordance with this hypothesis, we recorded SPM and SPD in pancreatic juice. The increases in PA concentrations seemed to follow the protein secretion pattern (i.e. PA concentrations reached a maximal value when the protein concentration was highest). The presence of PAs in pancreatic juice could be indicative of a control mechanism exerted by the pancreas on PA‐induced growth and differentiation of porcine intestinal epithelium.

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Polyamine transport in mammalian cells. An update

Cited by 333 publications

References 121 publications

Glypican-1 Is a Vehicle for Polyamine Uptake in Mammalian Cells

Glypican-1 Is a Vehicle for Polyamine Uptake in Mammalian Cells

Polyaminohydroxamic Acids and Polyaminobenzamides as Isoform Selective Histone Deacetylase Inhibitors

Pancreatic Exocrine Secretions as a Source of Luminal Polyamines in Pigs

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