Publications by authors named "Jumpei Sasabe"

Biomarkers that accurately reflect renal function are essential in management of chronic kidney diseases (CKD). However, in children, age/physique and medication often alter established renal biomarkers. We studied whether amino acid enantiomers in body fluids correlate with renal function and whether they are influenced by physique or steroid medication during development.

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Article Synopsis
  • - Transporter research usually focuses on well-known substrates, which limits understanding of how transporters work for less common micromolecules like micronutrients and d-serine, a potential kidney function biomarker.
  • - The study identifies two renal transport systems for d-serine: ASCT2, a previously unrecognized small amino acid transporter, and sodium-coupled monocarboxylate transporters (SMCTs), which reveals d-serine’s role as a non-canonical substrate.
  • - The findings show that ASCT2 is primarily responsible for d-serine transport, especially in pathological conditions, and highlight the need for broader research into the transport systems of trace micromolecules in health and disease contexts.
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Background & Aims: D-amino acids, the chiral counterparts of protein L-amino acids, were primarily produced and utilized by microbes, including those in the human gut. However, little was known about how orally administered or microbe-derived D-amino acids affected the gut microbial community or gut disease progression.

Methods: The ratio of D- to L-amino acids was analyzed in feces and blood from patients with ulcerative colitis (UC) and healthy controls.

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L-serine generated in astrocytes plays a pivotal role in modulating essential neurometabolic processes, while its enantiomer, D-serine, specifically regulates NMDA receptor (NMDAR) signalling. Despite their physiological relevance in modulating cerebral activity, serine enantiomers metabolism in Parkinson's disease (PD) remains elusive. Using High-Performance Liquid Chromatography (HPLC), we measured D- and L-serine levels along with other amino acids known to modulate NMDAR function, such as L-glutamate, L-aspartate, D-aspartate, and glycine, in the post-mortem caudate putamen (CPu) and superior frontal gyrus (SFG) of PD patients.

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The enteric nervous system (ENS) is a complex network of diverse molecularly defined classes of neurons embedded in the gastrointestinal wall and responsible for controlling the major functions of the gut. As in the central nervous system, the vast array of ENS neurons is interconnected by chemical synapses. Despite several studies reporting the expression of ionotropic glutamate receptors in the ENS, their roles in the gut remain elusive.

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Mammals exhibit systemic homochirality of amino acids in L-configurations. While ribosomal protein synthesis requires rigorous chiral selection for L-amino acids, both endogenous and microbial enzymes convert diverse L-amino acids to D-configurations in mammals. However, it is not clear how mammals manage such diverse D-enantiomers.

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Sodium benzoate (SB), a known D-amino acid oxidase (DAO) enzyme inhibitor, has an anti-inflammatory effect, although its role in renal damage has not been explored. 2,8-dihydroxyadenine crystal induced chronic kidney disease, in which TNF-α is involved in the pathogenesis, was established by oral adenine administration in C57BL/6JJcl mice (AdCKD) with or without SB to investigate its renal protective effects. SB significantly attenuated AdCKD by decreasing serum creatinine and urea nitrogen levels, and kidney interstitial fibrosis and tubular atrophy scores.

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Activation of N-methyl--aspartate receptors (NMDARs) requires binding of a co-agonist in addition to glutamate. serine binds to the co-agonist site on GluN1 subunits of NMDARs and modulates glutamatergic neurotransmission. While loss of GluN1 subunits in mice results in neonatal death due to respiratory failure, animals that lack a serine synthetic enzyme, serine racemase (SR), show grossly normal growth.

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d-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.

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Plasma amino acids reflect the dynamics of amino acids in organs and their levels have clinical significance. Amino acids as clinical indicators have been evaluated as a mixture of D- and L-amino acids because D-enantiomers are believed to be physiologically nonexistent. However, it has become clear that some D-amino acids are synthesized by endogenous enzymes and symbiotic bacteria.

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Organisms use l-amino acids (l-aa) for most physiological processes. Unlike other organisms, bacteria chiral-convert l-aa to d-configurations as essential components of their cell walls and as signaling molecules in their ecosystems. Mammals recognize microbe-associated molecules to initiate immune responses, but roles of bacterial d-amino acids (d-aa) in mammalian immune systems remain largely unknown.

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The mucin Muc2 is a major constituent of the mucus layer that covers the intestinal epithelium and creates a barrier between epithelial cells and luminal commensal or pathogenic microorganisms. The Gram-positive foodborne pathogen can cause enteritis and also disseminate from the intestine to give rise to systemic disease. can bind to intestinal Muc2, but the influence of the Muc2 mucin barrier on intestinal colonization and systemic dissemination has not been explored.

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Chiral separation has revealed enantio-specific changes in blood and urinary levels of amino acids in kidney diseases. Blood D-/L-serine ratio has been identified to have a correlation with creatinine-based kidney function. However, the mechanism of distinctive behavior in serine enantiomers is not well understood.

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Mammalian innate and adaptive immune systems use the pattern recognition receptors, such as toll-like receptors, to detect conserved bacterial and viral components. Bacteria synthesize diverse D-amino acids while eukaryotes and archaea generally produce two D-amino acids, raising the possibility that many of bacterial D-amino acids are bacteria-specific metabolites. Although D-amino acids have not been identified to bind to any known pattern recognition receptors, D-amino acids are enantioselectively recognized by some other receptors and enzymes including a flavoenzyme D-amino acid oxidase (DAO) in mammals.

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Living organisms enantioselectively employ L-amino acids as the molecular architecture of protein synthesized in the ribosome. Although L-amino acids are dominantly utilized in most biological processes, accumulating evidence points to the distinctive roles of D-amino acids in non-ribosomal physiology. Among the three domains of life, bacteria have the greatest capacity to produce a wide variety of D-amino acids.

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D-serine is an endogenous ligand for N-methyl-D-aspartate glutamate receptors. Accumulating evidence including genetic associations of D-serine metabolism with neurological or psychiatric diseases suggest that D-serine is crucial in human neurophysiology. However, distribution and regulation of D-serine in humans are not well understood.

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is a common food-borne pathogen that can disseminate from the intestine and infect multiple organs. Here, we used sequence tag-based analysis of microbial populations (STAMP) to investigate population dynamics during infection. We created a genetically barcoded library of murinized and then used deep sequencing to track the pathogen's dissemination routes and quantify its founding population () sizes in different organs.

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L-Amino acids are the building blocks for proteins synthesized in ribosomes in all kingdoms of life, but d-amino acids (d-aa) have important non-ribosome-based functions(1). Mammals synthesize d-Ser and d-Asp, primarily in the central nervous system, where d-Ser is critical for neurotransmission(2). Bacteria synthesize a largely distinct set of d-aa, which become integral components of the cell wall and are also released as free d-aa(3,4).

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Activity-based protein profiling (ABPP) is a chemoproteomic tool for detecting active enzymes in complex biological systems. We used ABPP to identify secreted bacterial and host serine hydrolases that are active in animals infected with the cholera pathogen Vibrio cholerae. Four V.

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Diverse environmental stimuli and a complex network of regulatory factors are known to modulate expression of Vibrio cholerae's principal virulence factors. However, there is relatively little known about how metabolic factors impinge upon the pathogen's well-characterized cascade of transcription factors that induce expression of cholera toxin and the toxin-coregulated pilus (TCP). Here, we used a transposon insertion site (TIS) sequencing-based strategy to identify new factors required for expression of tcpA, which encodes the major subunit of TCP, the organism's chief intestinal colonization factor.

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D-Serine is an essential coagonist with glutamate for stimulation of N-methyl-D-aspartate (NMDA) glutamate receptors. Although astrocytic metabolic processes are known to regulate synaptic glutamate levels, mechanisms that control D-serine levels are not well defined. Here we show that d-serine production in astrocytes is modulated by the interaction between the D-serine synthetic enzyme serine racemase (SRR) and a glycolytic enzyme, glyceraldehyde 3-phosphate dehydrogenase (GAPDH).

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D-Serine is an endogenous coagonist for N-methyl-D-aspartate (NMDA) receptors and is involved in excitatory neurotransmission. Excessive receptor activation causes excitotoxicity, leading to various acute and chronic neurological disorders. Decrease in D-serine content may provide a therapeutic strategy for the treatment of the neurological disorders in which overstimulation of NMDA receptors plays a pathological role.

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Horizontal dissemination of the genes encoding extended spectrum beta-lactamases (ESBLs) via conjugative plasmids is facilitating the increasingly widespread resistance of pathogens to beta-lactam antibiotics. However, there is relatively little known about the regulatory factors and mechanisms that govern the spread of these plasmids. Here, we carried out a high-throughput, transposon insertion site sequencing analysis (TnSeq) to identify genes that enable the maintenance and transmission of pESBL, an R64 (IncI1)-related resistance plasmid that was isolated from Escherichia coli O104:H4 linked to a recent large outbreak of gastroenteritis.

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