Human DJ-1 and its homologs are novel glyoxalases

• Published in: Human molecular genetics Vol. 21; no. 14; pp. 3215 - 3225
• Main Authors: LEE, Ju-Young, SONG, Jeeyeon, KWON, Kyu, SUMI JANG, KIM, Chayeon, BAEK, Kwanghee, KIM, Jeongho, PARK, Chankyu
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 15.07.2012
• Subjects: Age; Aldehyde Oxidoreductases - chemistry; Aldehyde Oxidoreductases - genetics; Aldehyde Oxidoreductases - metabolism; Amino Acid Sequence; Animals; Apoptosis; Biological and medical sciences; Caenorhabditis elegans; Caenorhabditis elegans - chemistry; Caenorhabditis elegans - enzymology; Caenorhabditis elegans - genetics; Caenorhabditis elegans Proteins - chemistry; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - metabolism; carbonyls; Cell Line; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Cysteine; Dopamine; Embryo fibroblasts; Fundamental and applied biological sciences. Psychology; Genetics of eukaryotes. Biological and molecular evolution; Glutamic acid; Glutathione; Glyoxal - metabolism; Humans; Intestine; Intracellular Signaling Peptides and Proteins - chemistry; Intracellular Signaling Peptides and Proteins - genetics; Intracellular Signaling Peptides and Proteins - metabolism; Kinetics; Lactic acid; Mice; Mice, Inbred C57BL; Mice, Knockout; Molecular and cellular biology; Molecular Sequence Data; Movement disorders; Neurodegeneration; Neurodegenerative diseases; Neurons; Neurons - cytology; Neurons - enzymology; Neurons - metabolism; Oncogene Proteins - chemistry; Oncogene Proteins - genetics; Oncogene Proteins - metabolism; PARK7 protein; Parkinson Disease - enzymology; Parkinson Disease - genetics; Parkinson Disease - metabolism; Parkinson's disease; Peroxiredoxins; Protein Deglycase DJ-1; Pyruvaldehyde; Pyruvaldehyde - metabolism; Rats; Sequence Alignment; Human; Genetics; C-Onc gene; Protooncogene
• ISSN: 0964-6906; 1460-2083
• DOI: 10.1093/hmg/dds155

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.