期刊
BIOCHEMICAL JOURNAL
卷 450, 期 -, 页码 47-53出版社
PORTLAND PRESS LTD
DOI: 10.1042/BJ20120739
关键词
Parkinson's disease; P-5B-ATPase type 13A2 (P-5B-ATP13A2); polyamine; polyamine transport system; P-type ATPase; spermidine uptake
资金
- University of Buenos Aires (UBA) [B604]
- Consejo Nacional de Investigaciones Cientfficas y TOcnicas (CONICET) [PIP 112-200801-02022]
- Agencia Nacional de Promockin Cientffica y TecnolOgica (ANPCyT) [BID PICT 2007-702, ANPCyT and BID PICT 2008-02134]
P-type ion pumps are membrane transporters that have been classified into five subfamilies termed P-1-P-5. The ion transported by the P-5-ATPases is not known. Five genes, ATP13A (ATPase type 13A) 1-ATP13A5, that belong to the P-5-ATPase group have been identified in humans Mutations of the human gene ATP13A2 underlie a form of PD (Parkinson's disease). Previous studies have suggested a relation between polyamines and P-5B-ATPases. We have recently shown that the cytotoxicity induced by the polyamine analogue paraquat (1,1'-dimethy1-4,4'-bipyridinium), which is an environmental agent related to PD development, was increased in ATP13A2-expressing CHO (Chinese-hamster ovary) cells. In the present study we showed that ATP13A2-expressing CHO cells exhibit a 2-fold higher accumulation of spermidine. Increasing concentrations of spermidine reduced the viability of CHO cells stably expressing ATP13A2. The higher levels of spermidine attained by the ATP13A2-expressing CHO cells were correlated with an increase in the ATP-dependent spermidine uptake in an isolated subcellular fraction containing lysosomes and late endosomes. The results of the present study support the idea that the human P-5B-ATPase ATP13A2 is involved in polyamine uptake.
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