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Silencing DJ‐1 reveals its contribution in paraquat‐induced autophagy
Author(s) -
GonzálezPolo Rosa A.,
NisoSantano Mireia,
Morán José M.,
OrtizOrtiz Miguel A.,
BravoSan Pedro José M.,
Soler Germán,
Fuentes José M.
Publication year - 2009
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2009.06020.x
Subject(s) - autophagy , paraquat , vacuole , biology , programmed cell death , microbiology and biotechnology , gene silencing , small interfering rna , apoptosis , cancer research , transfection , cytoplasm , cell culture , genetics , gene , biochemistry
J. Neurochem . (2009) 109 , 889–898. Abstract The role of autophagy as a survival strategy of cells constitutes an emerging topic in the study of the pathogenesis of several diseases with autophagic changes being described in a number of age‐related neurodegenerative disorders, including Parkinson’s disease (PD). Although the etiology of PD is still unknown, both environmental (for example, paraquat exposure) and genetic factors have been investigated as putative causes of the disease. In the latter case, mutations or changes in the protein DJ‐1 have been reported to be associated with autosomal recessive, early‐onset parkinsonism. In this paper we established a model system to study the involvement of the DJ‐1 protein in paraquat‐induced autophagy. When human neuroblastoma SH‐SY5Y cells were transfected with DJ‐1‐specific small interfering RNAs and exposed to paraquat, we observed (i) sensitization additive with paraquat‐induced apoptotic cell death, (ii) inhibition of the cytoplasmic accumulation of autophagic vacuoles as well as the recruitment of LC3 fusion protein to the vacuoles, (iii) exacerbation of apoptotic cell death in the presence of the autophagy inhibitor 3‐methyladenine, and (iv) an increase in mammalian target of rapamycin phosphorylation. Taken together, these findings suggest an active role for DJ‐1 in the autophagic response produced by paraquat, providing evidence for the role of PD‐related proteins in the autophagic degradation pathway, a factor that should be considered in the design of potential therapies for the treatment of the disease.