scholarly journals ATP13A3 is a major component of the enigmatic mammalian polyamine transport system

2020 ◽  
pp. jbc.RA120.013908
Author(s):  
Norin Nabil Hamouda ◽  
Chris Van den Haute ◽  
Roeland Vanhoutte ◽  
Ragna Sannerud ◽  
Mujahid Azfar ◽  
...  
Keyword(s):  
Transport System ◽  
Mammalian Cells ◽  
Polyamine Biosynthesis ◽  
Polyamine Transport System ◽  
Polyamine Transport ◽  
Mrna And Protein Expression ◽  
Transport Inhibitors ◽  
Pulmonary Arterial ◽  
Polyamine Uptake ◽  
P Type

Polyamines, such as putrescine, spermidine and spermine, are physiologically important polycations, but the transporters responsible for their uptake in mammalian cells remain poorly characterized. Here, we reveal a new component of the mammalian polyamine transport system (PTS) using CHO-MG cells, a widely used model to study alternative polyamine uptake routes and characterize polyamine transport inhibitors for therapy. CHO-MG cells present polyamine uptake deficiency and resistance to a toxic polyamine biosynthesis inhibitor MGBG (methylglyoxal bis- (guanylhydrazone)), but the molecular defects responsible for these cellular characteristics remain unknown. By genome sequencing of CHO-MG cells, we identified mutations in an unexplored gene, ATP13A3, and found disturbed mRNA and protein expression. ATP13A3 encodes for an orphan P5B-ATPase (ATP13A3), a P-type transport ATPase that represents a candidate polyamine transporter. Interestingly, ATP13A3 complemented the putrescine transport deficiency and MGBG resistance of CHO-MG cells, whereas its knockdown in wild-type cells induced a CHO-MG phenotype, demonstrating a decrease in putrescine uptake and MGBG sensitivity. Taken together, our findings identify ATP13A3 as a major component of the mammalian PTS that confers sensitivity to MGBG and that has been previously genetically linked with pulmonary arterial hypertension.

scholarly journals Feedback repression of polyamine transport is mediated by antizyme in mammalian tissue-culture cells

1994 ◽  
Vol 299 (1) ◽  
pp. 19-22 ◽  
Author(s):  
J L Mitchell ◽  
G G Judd ◽  
A Bareyal-Leyser ◽  
S Y Ling
Keyword(s):  
Ornithine Decarboxylase ◽  
Mammalian Cells ◽  
Feedback Inhibition ◽  
Mammalian Tissue ◽  
Polyamine Biosynthesis ◽  
Culture Cells ◽  
Tissue Culture Cells ◽  
Polyamine Transport ◽  
A Cell ◽  
Polyamine Uptake

Antizyme, a spermidine-induced protein that binds and stimulates ornithine decarboxylase degradation, is now shown also to mediate the rapid feedback inhibition of polyamine uptake into mammalian cells. Using a cell line (HZ7) transfected with truncated antizyme cDNA, and mutant ornithine decarboxylase cell lines, we demonstrate that this newly discovered action of antizyme is distinct from its role in modulating polyamine biosynthesis.

scholarly journals bis(benzyl)polyamine analogues are substrates for a mammalian cell-transport system which is distinct from the polyamine-transport system

1990 ◽  
Vol 269 (1) ◽  
pp. 35-40 ◽  
Author(s):  
T L Byers ◽  
A J Bitonti ◽  
P P McCann
Keyword(s):  
Mammalian Cell ◽  
Transport System ◽  
Cho Cells ◽  
Chinese Hamster ◽  
Polyamine Biosynthesis ◽  
Cell Transport ◽  
Polyamine Analogues ◽  
Polyamine Transport System ◽  
Polyamine Transport ◽  
Htc Cells

Bis(benzyl)polyamine analogues (e.g. NN′-bis(3-[(phenylmethyl)amino]propyl)-1,8-diamino-octane [C6H5CH2NH-(CH2)3NH(CH2)8NH(CH2)3NHCH2C6H5]) have previously been shown to regulate polyamine biosynthesis and growth of rat hepatoma (HTC) cells. Saturable uptake of the analogues, the ability of other bis(benzyl)polyamine analogues to compete for this uptake and the trans-acceleration of this uptake in pre-loaded cells indicate that these novel compounds are accumulated through the action of a transport system in HTC cells. A mutant Chinese-hamster-ovary (CHO) cell line, CHOMG, which lacks a functional polyamine-transport system, exhibited saturable bis(benzyl)polyamine uptake identical with that observed in the parental CHO cells, which have normal polyamine transport. The uptake of the analogue by both CHOMG and CHO cells was competitively inhibited by other bis(benzyl)polyamine analogues, but was insensitive to excess spermine. Treatment with alpha-difluoromethylornithine, an inhibitor of polyamine biosynthesis, resulted in the enhancement of spermine uptake in CHO cells but did not alter the uptake of a bis(benzyl)polyamine analogue by either CHO or CHOMG cells. Thus it appears that bis(benzyl)polyamine analogues are substrates for a mammalian-cell-transport system distinct from the polyamine-transport system.

Polyamine transport system-targeted nanometric micelles assembled from epipodophyllotoxin-amphiphiles

2019 ◽  
Vol 55 (99) ◽  
pp. 14968-14971 ◽  
Author(s):  
Julien Alliot ◽  
Ioanna Theodorou ◽  
Frédéric Ducongé ◽  
Edmond Gravel ◽  
Eric Doris
Keyword(s):  
Transport System ◽  
Biologically Active ◽  
Drug Conjugates ◽  
Amphiphilic Drug ◽  
Polyamine Transport System ◽  
Polyamine Transport

Micelle-forming amphiphilic drug conjugates were synthesized starting from a biologically active epipodophyllotoxin derivative which was covalently inserted in between a hydrophilic targeting spermine unit, and a hydrophobic stearyl chain.

Pulmonary alveolar macrophages express a polyamine transport system

1989 ◽  
Vol 139 (3) ◽  
pp. 624-631 ◽  
Author(s):  
Nicholas A. Saunders ◽  
Kenneth F. Ilett ◽  
Rodney F. Minchin
Keyword(s):  
Transport System ◽  
Alveolar Macrophages ◽  
Polyamine Transport System ◽  
Polyamine Transport ◽  
Pulmonary Alveolar Macrophages

Paraquat is not accumulated in B16 tumor cells by the polyamine transport system

Life Sciences ◽  
1989 ◽  
Vol 45 (1) ◽  
pp. 63-69 ◽  
Author(s):  
Rodney F. Minchin ◽  
Roger L. Martin ◽  
Kenneth F. Ilett
Keyword(s):  
Tumor Cells ◽  
Transport System ◽  
Polyamine Transport System ◽  
Polyamine Transport

Polyamine transport system mediates agmatine transport in mammalian cells

2001 ◽  
Vol 281 (1) ◽  
pp. C329-C334 ◽  
Author(s):  
Joseph Satriano ◽  
Masato Isome ◽  
Robert A. Casero ◽  
Scott C. Thomson ◽  
Roland C. Blantz
Keyword(s):  
Transport System ◽  
Mammalian Cells ◽  
Maximal Velocity ◽  
Human Carcinoma ◽  
Mammalian Cell Lines ◽  
Carrier Mediated Transport ◽  
Polyamine Transport ◽  
Polyamine Content ◽  
Polyamine Transporter ◽  
Nih 3T3

Agmatine is a biogenic amine with the capacity to regulate a number of nonreceptor-mediated functions in mammalian cells, including intracellular polyamine content and nitric oxide generation. We observed avid incorporation of agmatine into several mammalian cell lines and herein characterize agmatine transport in mammalian cells. In transformed NIH/3T3 cells, agmatine uptake is energy dependent with a saturable component indicative of carrier-mediated transport. Transport displays an apparent Michaelis-Menten constant of 2.5 μM and a maximal velocity of 280 pmol · min−1 · mg−1 protein and requires a membrane potential across the plasma membrane for uptake. Competition with polyamines, but not cationic molecules that utilize the y+ system transporter, suppresses agmatine uptake. Altering polyamine transporter activity results in parallel changes in polyamine and agmatine uptake. Furthermore, agmatine uptake is abrogated in a polyamine transport-deficient human carcinoma cell line. These lines of evidence demonstrate that agmatine utilizes, and is dependent on, the polyamine transporter for cellular uptake. The fact that this transport system is associated with proliferation could be of consequence to the antiproliferative effects of agmatine.

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