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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Aldehyde Oxidoreductases / chemistry
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Aldehyde Oxidoreductases / genetics
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Aldehyde Oxidoreductases / metabolism*
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Amino Acid Sequence
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Animals
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Apoptosis
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Caenorhabditis elegans / chemistry
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Caenorhabditis elegans / enzymology*
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Caenorhabditis elegans / genetics
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Caenorhabditis elegans Proteins / chemistry
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Caenorhabditis elegans Proteins / genetics
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Caenorhabditis elegans Proteins / metabolism*
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Cell Line
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Glyoxal / metabolism
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Humans
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Intracellular Signaling Peptides and Proteins / chemistry
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Intracellular Signaling Peptides and Proteins / genetics
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Intracellular Signaling Peptides and Proteins / metabolism*
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Kinetics
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Molecular Sequence Data
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Neurons / cytology
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Neurons / enzymology
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Neurons / metabolism
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Oncogene Proteins / chemistry
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Oncogene Proteins / genetics
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Oncogene Proteins / metabolism*
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Parkinson Disease / enzymology*
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Parkinson Disease / genetics
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Parkinson Disease / metabolism
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Peroxiredoxins
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Protein Deglycase DJ-1
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Pyruvaldehyde / metabolism
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Rats
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Sequence Alignment
Substances
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Caenorhabditis elegans Proteins
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Intracellular Signaling Peptides and Proteins
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Oncogene Proteins
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Glyoxal
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Pyruvaldehyde
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Peroxiredoxins
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Aldehyde Oxidoreductases
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DJR-1.1 protein, C elegans
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DJR-1.2 protein, C elegans
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glyoxalase III
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PARK7 protein, human
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PARK7 protein, mouse
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Protein Deglycase DJ-1