Pinthong_2008_Mol.Pharmacol_73_801

Reference

Title : Activity and subcellular trafficking of the sodium-coupled choline transporter CHT is regulated acutely by peroxynitrite - Pinthong_2008_Mol.Pharmacol_73_801
Author(s) : Pinthong M , Black SA , Ribeiro FM , Pholpramool C , Ferguson SS , Rylett RJ
Ref : Molecular Pharmacology , 73 :801 , 2008
Abstract :

Excess formation of nitric oxide and superoxide by-products (peroxynitrite, reactive oxygen, and reactive nitrogen species) attenuates cholinergic transmission potentially having a role in Alzheimer disease pathogenesis. In this study, we investigated mechanisms by which acute exposure to peroxynitrite impairs function of the sodium-dependent hemicholinium-3 (HC-3)-sensitive choline transporter (CHT) that provides substrate for acetylcholine synthesis. The peroxynitrite generator 3-morpholinosydnonimine (SIN-1) acutely inhibited choline uptake in cells stably expressing FLAG-tagged rat CHT in a dose- and time-dependent manner, with an IC(50) = 0.9 +/- 0.14 mM and t((1/2)) = 4 min. SIN-1 significantly reduced V(max) of choline uptake without altering the K(m). This correlated with a SIN-1-induced decrease in cell surface CHT protein, observed as lowered levels of HC-3 binding and biotinylated CHT at the plasma membrane. It is noteworthy that short-term exposure of cells to SIN-1 accelerated the rate of internalization of CHT from the plasma membrane, but it did not alter return of CHT back to the cell surface. SIN-1 did not disrupt cell membrane integrity or cause cell death. Thus, the inhibitory effect of SIN-1 on choline uptake activity and HC-3 binding was related to enhanced internalization of CHT proteins from the plasma membrane to subcellular organelles.

PubMedSearch : Pinthong_2008_Mol.Pharmacol_73_801
PubMedID: 17971421

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Citations formats

Pinthong M, Black SA, Ribeiro FM, Pholpramool C, Ferguson SS, Rylett RJ (2008)
Activity and subcellular trafficking of the sodium-coupled choline transporter CHT is regulated acutely by peroxynitrite
Molecular Pharmacology 73 :801

Pinthong M, Black SA, Ribeiro FM, Pholpramool C, Ferguson SS, Rylett RJ (2008)
Molecular Pharmacology 73 :801