Human DJ-1 and its homologs are novel glyoxalases

Cited 131 time in webofscience Cited 0 time in scopus
  • Hit : 546
  • Download : 0
Human DJ-1 is a genetic cause of early-onset Parkinsons disease (PD), although its biochemical function is unknown. We report here that human DJ-1 and its homologs of the mouse and Caenorhabditis elegans are novel types of glyoxalase, converting glyoxal or methylglyoxal to glycolic or lactic acid, respectively, in the absence of glutathione. Purified DJ-1 proteins exhibit typical MichaelisMenten kinetics, which were abolished completely in the mutants of essential catalytic residues, consisting of cysteine and glutamic acid. The presence of DJ-1 protected mouse embryonic fibroblast and dopaminergically derived SH-SY5Y cells from treatments of glyoxals. Likewise, C. elegans lacking cDJR-1.1, a DJ-1 homolog expressed primarily in the intestine, protected worms from glyoxal-induced death. Sub-lethal doses of glyoxals caused significant degeneration of the dopaminergic neurons in C. elegans lacking cDJR-1.2, another DJ-1 homolog expressed primarily in the head region, including neurons. Our findings that DJ-1 serves as scavengers for reactive carbonyl species may provide a new insight into the causation of PD.
Publisher
OXFORD UNIV PRESS
Issue Date
2012-07
Language
English
Article Type
Article
Keywords

PARKINSONS-DISEASE; OXIDATIVE STRESS; CAENORHABDITIS-ELEGANS; ESCHERICHIA-COLI; ALPHA-SYNUCLEIN; PROTEIN DJ-1; MITOCHONDRIAL LOCALIZATION; DOPAMINERGIC-NEURONS; CRYSTAL-STRUCTURE; GLYCATION

Citation

HUMAN MOLECULAR GENETICS, v.21, no.14, pp.3215 - 3225

ISSN
0964-6906
DOI
10.1093/hmg/dds155
URI
http://hdl.handle.net/10203/103925
Appears in Collection
BS-Journal Papers(저널논문)
Files in This Item
There are no files associated with this item.
This item is cited by other documents in WoS
⊙ Detail Information in WoSⓡ Click to see webofscience_button
⊙ Cited 131 items in WoS Click to see citing articles in records_button

qr_code

  • mendeley

    citeulike


rss_1.0 rss_2.0 atom_1.0