RT info:eu-repo/semantics/article
T1 The dopamine transporter is differentially regulated after dopaminergic lesion
A1 Castro Hernández, Javier Rafael
A1 Afonso Oramas, Domingo
A1 Cruz Muros, Ignacio
A1 Barroso Chinea, Pedro
A1 Álvarez de la Rosa, Diego
A1 Salas Hernández, Josmar
A1 Giráldez, Teresa
A1 González Hernández, Tomás
A2 Medicina Física y Farmacología
A2 Vulnerabilidad y plasticidad neuronal
K1 Parkinson's disease
K1 Vulnerability
K1 Mesostriatal
K1 Degeneration
K1 Dopamine transporter
K1 Rat
K1 HEK-cell
K1 6-OHDA
K1 MPP
AB The dopamine transporter (DAT) is a transmembrane glycoprotein responsible for dopamine (DA) uptake,which has been shown to be involved in DA-cell degeneration in Parkinson's disease (PD). At the same time,some studies suggest that DAT may be regulated in response to dopaminergic injury. We have investigatedthe mechanisms underlying DAT regulation after different degrees of dopaminergic lesion. DAT ispersistently down-regulated in surviving midbrain DA-neurons after substantial (62%) loss of striatal DAterminals, and transiently after slight (11%) loss of DA-terminals in rats. Transient DAT down-regulationconsisted of a decrease of glycosylated (mature) DAT in the plasma membrane with accumulation of nonglycosylated (immature) DAT in the endoplasmic reticulum-Golgi (ERG) compartment, and recovery of thenormal expression pattern 5 days after lesion. DAT redistribution to the ERG was also observed in HEK cellsexpressing rat DAT exposed to MPP+, but not after exposure to DAT-unrelated neurotoxins. In contrast toother midbrain DA-cells, those in the ventrolateral region of the substantia nigra do not regulate DAT anddegenerate shortly after slight DA-lesion. These data suggest that DAT down-regulation is a post-traslationalevent induced by DA-analogue toxins, consisting of a stop in its glycosylation and trafficking to the plasmamembrane. Its persistence after substantial DA-lesion may act as a compensatory mechanism helpingmaintain striatal DA levels. The fact that neurons which do not regulate DAT die shortly after lesion suggestsa relationship between DAT down-regulation and neuroprotection.
YR 2010
FD 2010
LK http://riull.ull.es/xmlui/handle/915/34773
UL http://riull.ull.es/xmlui/handle/915/34773
LA en
DS Repositorio institucional de la Universidad de La Laguna
RD 22-nov-2024