title: Human DJ-1 and its homologs are novel glyoxalases.
abstract: Human DJ-1 is a genetic cause of early-onset Parkinson's 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 Michaelis-Menten 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.
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Yuseong-gu, Daejeon 305-701, Republic of Korea.
authors.forename: Ju-young
authors.initials: JY
authors.lastname: Lee
authors.forename: Jeeyeon
authors.initials: J
authors.lastname: Song
authors.forename: Kyu
authors.initials: K
authors.lastname: Kwon
authors.forename: Sumi
authors.initials: S
authors.lastname: Jang
authors.forename: Chayeon
authors.initials: C
authors.lastname: Kim
authors.forename: Kwanghee
authors.initials: K
authors.lastname: Baek
authors.forename: Jeongho
authors.initials: J
authors.lastname: Kim
authors.forename: Chankyu
authors.initials: C
authors.lastname: Park
mesh_terms: D000445:Aldehyde Oxidoreductases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D017173:Caenorhabditis elegans / Q000737:chemistry / Q000201:enzymology* / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D006037:Glyoxal / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D007700:Kinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009474:Neurons / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D015513:Oncogene Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010300:Parkinson Disease / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D054464:Peroxiredoxins; D000071617:Protein Deglycase DJ-1; D011765:Pyruvaldehyde / Q000378:metabolism; D051381:Rats; D016415:Sequence Alignment
chemical_list: D029742:Caenorhabditis elegans Proteins; D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; D006037:Glyoxal; D011765:Pyruvaldehyde; D054464:Peroxiredoxins; D000445:Aldehyde Oxidoreductases; C577306:DJR-1.1 protein, C elegans; C577307:DJR-1.2 protein, C elegans; C091855:glyoxalase III; C105131:PARK7 protein, human; C503466:PARK7 protein, mouse; D000071617:Protein Deglycase DJ-1