論文 - 詳細
RRC ID | 17582 |
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著者 | Lee JY, Song J, Kwon K, Jang S, Kim C, Baek K, Kim J, Park C. |
タイトル | Human DJ-1 and its homologs are novel glyoxalases. |
ジャーナル | Hum Mol Genet |
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. |
巻・号 | 21(14) |
ページ | 3215-25 |
公開日 | 2012-7-15 |
DOI | 10.1093/hmg/dds155 |
PII | dds155 |
PMID | 22523093 |
MeSH | Aldehyde Oxidoreductases / chemistry Aldehyde Oxidoreductases / genetics Aldehyde Oxidoreductases / metabolism* Amino Acid Sequence Animals Apoptosis Caenorhabditis elegans / chemistry Caenorhabditis elegans / enzymology* Caenorhabditis elegans / genetics Caenorhabditis elegans Proteins / chemistry Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Cell Line Glyoxal / metabolism Humans Intracellular Signaling Peptides and Proteins / chemistry Intracellular Signaling Peptides and Proteins / genetics Intracellular Signaling Peptides and Proteins / metabolism* Kinetics Mice Mice, Inbred C57BL Mice, Knockout Molecular Sequence Data Neurons / cytology Neurons / enzymology Neurons / metabolism Oncogene Proteins / chemistry Oncogene Proteins / genetics Oncogene Proteins / metabolism* Parkinson Disease / enzymology* Parkinson Disease / genetics Parkinson Disease / metabolism Peroxiredoxins Protein Deglycase DJ-1 Pyruvaldehyde / metabolism Rats Sequence Alignment |
IF | 5.101 |
引用数 | 117 |
WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY GENETICS & HEREDITY |
リソース情報 | |
線虫 | tm918 tm1346 |