TY - JOUR
T1 - Parkinson disease-associated DJ-1 is required for the expression of the glial cell line-derived neurotrophic factor receptor RET in human neuroblastoma cells
AU - Foti, Rossana
AU - Zucchelli, Silvia
AU - Biagioli, Marta
AU - Roncaglia, Paola
AU - Vilotti, Sandra
AU - Calligaris, Raffaella
AU - Krmac, Helena
AU - Girardini, Javier Enrique
AU - Del Sal, Giannino
AU - Gustincich, Stefano
PY - 2010/6/11
Y1 - 2010/6/11
N2 - Mutations in PARK7/DJ-1 are associated with autosomal recessive, early onset Parkinson disease (PD). DJ-1 is an atypical peroxiredoxin-like peroxidase that may act as a redox-dependent chaperone and a regulator of transcription. Here we show that DJ-1 plays an essential role in the expression of rearranged during transfection (RET), a receptor for the glial cell line-derived neurotrophic factor, a neuroprotective molecule for dopaminergic neurons, the main target of degeneration in PD. The inducible loss of DJ-1 triggers the establishment of hypoxia and the production of reactive oxygen species that stabilize the hypoxia-inducible factor-1α (HIF-1a). HIF-1a expression is required for RET down-regulation. This study establishes for the first time a molecular link between the lack of functional DJ-1 and the glial cell line-derived neurotrophic factor signaling pathway that may explain the adult-onset loss of dopaminergic neurons. Furthermore, it suggests that hypoxia may play an important role in PD.
AB - Mutations in PARK7/DJ-1 are associated with autosomal recessive, early onset Parkinson disease (PD). DJ-1 is an atypical peroxiredoxin-like peroxidase that may act as a redox-dependent chaperone and a regulator of transcription. Here we show that DJ-1 plays an essential role in the expression of rearranged during transfection (RET), a receptor for the glial cell line-derived neurotrophic factor, a neuroprotective molecule for dopaminergic neurons, the main target of degeneration in PD. The inducible loss of DJ-1 triggers the establishment of hypoxia and the production of reactive oxygen species that stabilize the hypoxia-inducible factor-1α (HIF-1a). HIF-1a expression is required for RET down-regulation. This study establishes for the first time a molecular link between the lack of functional DJ-1 and the glial cell line-derived neurotrophic factor signaling pathway that may explain the adult-onset loss of dopaminergic neurons. Furthermore, it suggests that hypoxia may play an important role in PD.
UR - http://www.scopus.com/inward/record.url?scp=77953316340&partnerID=8YFLogxK
U2 - 10.1074/jbc.M109.088294
DO - 10.1074/jbc.M109.088294
M3 - Article
SN - 0021-9258
VL - 285
SP - 18565
EP - 18574
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 24
ER -