Human DJ-1 and its homologs are novel glyoxalases

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 a...

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Published inHuman 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
LanguageEnglish
Published Oxford Oxford University Press 15.07.2012
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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.
AbstractList 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.
Author BAEK, Kwanghee
PARK, Chankyu
SUMI JANG
KIM, Jeongho
LEE, Ju-Young
KWON, Kyu
SONG, Jeeyeon
KIM, Chayeon
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  surname: SUMI JANG
  fullname: SUMI JANG
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  fullname: PARK, Chankyu
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Snippet 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...
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StartPage 3215
SubjectTerms 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
Title Human DJ-1 and its homologs are novel glyoxalases
URI https://www.ncbi.nlm.nih.gov/pubmed/22523093
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https://search.proquest.com/docview/1028031893
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