Determination of d-serine and d-alanine in the tissues and physiological fluids of mice with various d-amino-acid oxidase activities using two-dimensional high-performance liquid chromatography with fluorescence detection

Miyoshi, Y.; Hamase, Kenji; Tojo, Yosuke; Mita, Masashi; Konno, Ryuichi; Zaitsu, Kiyoshi

doi:10.1016/j.jchromb.2009.06.028

Cited by 131 publications

(175 citation statements)

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“…The five target D-amino acids were selected because these D-amino acids are frequently observed in higher animals (as their free forms) [2][3][4][5]. In the first dimension, the five target NBD-amino acids were separated using a capillary monolithic ODS column, and the elution conditions were optimized.…”

Section: Establishment Of An Enantioselective Two-dimensional Hplc-msmentioning

confidence: 99%

“…All proteinogenic amino acids, except glycine, have optical isomers (enantiomers), namely the D-and L-forms, and L-amino acids are predominant in the higher animals. However, from the 1980s, several D-amino acids have been reported to be present as their free forms in mammalian tissues including human beings, and these D-amino acids are expected to be novel physiologically active substances and biomarkers [1][2][3][4][5]. In the proteins and peptides, D-amino acid residues, especially D-Asp, have also been reported in various disease/aged proteins including Alzheimer's disease and cataract [6][7][8][9][10][11][12].…”

Section: Introductionmentioning

confidence: 99%

“…In the present study, an analytical method has been established for the determination of D-Ala, D-Asp, D-Glu, D-Pro and D-Ser (these 5 D-amino acids are frequently observed in vertebrates [2][3][4][5]) residues in protein samples. For the analysis, a two-dimensional HPLC-MS/MS system was adopted after the DCl/D 2 O hydrolysis.…”

Section: Introductionmentioning

confidence: 99%

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Establishment of a Two-Dimensional HPLC-MS/MS Method Combined with DCl/D<sub>2</sub>O Hydrolysis for the Determination of Trace Amounts of D-Amino Acid Residues in Proteins

Ishigo

Negishi²,

Miyoshi

et al. 2015

Chromatography

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A two-dimensional (2D) HPLC-MS/MS method has been established for the determination of trace amounts of D-amino acid residues in proteins. D-Amino acid residues are now increasingly recognized as biomarkers of diseases and key moieties for the regulation of protein structures/functions, therefore, a sensitive analytical method is highly required. However, non-negligible amounts of D-amino acids are produced by chemical racemization during the hydrolysis of proteins, and a sensitive determination of D-amino acid residues is normally difficult. In the present study, DCl/D 2 O hydrolysis is adopted and the produced deuterated D-amino acids are distinguished from naturally-occurring D-amino acids in the proteins using the 2D-HPLC-MS/MS system. D-Ala, D-Asp, D-Glu, D-Pro and D-Ser (frequently observed D-amino acids in higher animals) were selected as the targets, and the sensitive determination (around 1% or less of the L-forms) could be carried out. As an application, the D-amino acid residues in ovalbumin (OVA) were determined, and the presence of a significant amount of D-Ser (1.8% of L-Ser) was demonstrated.

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Section: Establishment Of An Enantioselective Two-dimensional Hplc-msmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Establishment of a Two-Dimensional HPLC-MS/MS Method Combined with DCl/D<sub>2</sub>O Hydrolysis for the Determination of Trace Amounts of D-Amino Acid Residues in Proteins

Ishigo

Negishi²,

Miyoshi

et al. 2015

Chromatography

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“…If D-serine synthesis through L-serine increase and up-regulation of SRR (Fig. S5) (10) (18,19,21), as a control D-amino acid that is not metabolized by DAO. Genetic inactivation of DAO markedly increased the D-alanine level, whereas D-aspartate was not affected at all (Fig.…”

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confidence: 99%

“…To evaluate each contribution, we measured the amount of D-/L-serine with a 2D-HPLC system, a highly selective and sensitive method ( Fig. S4 and Materials and Methods) (18,19). The D-serine level in the spinal cord is negatively correlated with the activity of DAO (Fig.…”

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confidence: 99%

d -Amino acid oxidase controls motoneuron degeneration through d -serine

Sasabe

Miyoshi

Suzuki

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder involving an extensive loss of motoneurons. Aberrant excitability of motoneurons has been implicated in the pathogenesis of selective motoneuronal death in ALS. D-Serine, an endogenous coagonist of N-methyl-D-aspartate receptors, exacerbates motoneuronal death and is increased both in patients with sporadic/ familial ALS and in a G93A-SOD1 mouse model of ALS (mSOD1 mouse). More recently, a unique mutation in the D-amino acid oxidase (DAO) gene, encoding a D-serine degrading enzyme, was reported to be associated with classical familial ALS. However, whether DAO affects the motoneuronal phenotype and D-serine increase in ALS remains uncertain. Here, we show that genetic inactivation of DAO in mice reduces the number and size of lower motoneurons with axonal degeneration, and that suppressed DAO activity in reactive astrocytes in the reticulospinal tract, one of the major inputs to the lower motoneurons, predominantly contributes to the D-serine increase in the mSOD1 mouse. The DAO inactivity resulted from expressional down-regulation, which was reversed by inhibitors of a glutamate receptor and MEK, but not by those of inflammatory stimuli. Our findings provide evidence that DAO has a pivotal role in motoneuron degeneration through D-serine regulation and that inactivity of DAO is a common feature between the mSOD1 ALS mouse model and the mutant DAO-associated familial ALS. The therapeutic benefit of reducing D-serine or controlling DAO activity in ALS should be tested in future studies.excitotoxicity | motor neuron disease | neurodegeneration | enzyme histochemistry | 2D-HPLC A myotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by selective loss of motoneurons in the spinal cord and brain leading to fatal paralysis. Approximately 90% of all cases are sporadic, and the remaining cases are inherited. Of inherited cases, 20% are associated with mutations in superoxide dismutase 1 (SOD1), and 10% involves 43-kDa transactivation response DNA-binding protein (TDP-43) and fused in sarcoma/translocated in liposarcoma (FUS/TLS). Despite extensive studies of previously identified ALS-causing genes, the mechanism underlying the selective motoneuronal loss in ALS remains uncertain. Given that the mechanism is at least, in part, common between sporadic and familial ALS, identification of the common pathology is a clue to conquering ALS. Among numerous etiological hypotheses, motoneuronal vulnerability to excitotoxicity is one of the most intensely investigated targets for the treatment of ALS because it is observed in both sporadic and familial ALS with SOD1 mutations (1, 2). For motoneurons, glutamate is the main excitatory transmitter, and excessive motoneuron excitability by glutamate through ionotropic glutamate receptors has been demonstrated.The N-methyl-D-aspartate (NMDA) receptor (NMDAR) is a subtype of the ionotropic glutamate receptors and exhibits relatively higher permeability to the calcium ion (Ca ...

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Astrocytic d‐amino acid oxidase degrades d‐serine in the hindbrain

Gonda¹,

Ishii

Mita

et al. 2022

FEBS Letters

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Edited by Ned ManteiD-Serine modulates excitatory neurotransmission by binding to N-methyl-D-aspartate glutamate receptors. D-Amino acid oxidase (DAO) degrades D-amino acids, such as D-serine, in the central nervous system, and is associated with neurological and psychiatric disorders. However, cell types that express brain DAO remain controversial, and whether brain DAO influences systemic D-amino acids in addition to brain D-serine remains unclear. Here, we created astrocyte-specific DAO-conditional knockout mice. Knockout in glial fibrillary acidic protein-positive cells eliminated DAO expression in the hindbrain and increased D-serine levels significantly in the cerebellum. Brain DAO did not influence levels of D-amino acids in the forebrain or periphery. These results show that astrocytic DAO regulates D-serine specifically in the hindbrain.

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Determination of d-serine and d-alanine in the tissues and physiological fluids of mice with various d-amino-acid oxidase activities using two-dimensional high-performance liquid chromatography with fluorescence detection

Cited by 131 publications

References 42 publications

Establishment of a Two-Dimensional HPLC-MS/MS Method Combined with DCl/D<sub>2</sub>O Hydrolysis for the Determination of Trace Amounts of D-Amino Acid Residues in Proteins

Establishment of a Two-Dimensional HPLC-MS/MS Method Combined with DCl/D<sub>2</sub>O Hydrolysis for the Determination of Trace Amounts of D-Amino Acid Residues in Proteins

d -Amino acid oxidase controls motoneuron degeneration through d -serine

Astrocytic d‐amino acid oxidase degrades d‐serine in the hindbrain

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