Hypotaurine Is a Substrate of GABA Transporter Family Members GAT2/Slc6a13 and TAUT/Slc6a6

Nishimura, Tomohiro; Higuchi, Kei; Yoshida, Yasuhiko; Sugita-Fujisawa, Yuki; Kojima, Kazuyuki; Sugimoto, M.; Santo, Marie; Tomi, Masatoshi; Nakashima, Emi

doi:10.1248/bpb.b18-00168

Cited by 14 publications

(13 citation statements)

References 35 publications

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“…6). These two compounds are related to the gene SLC6A13 as either substrates (hypotaurine) or derivative of a substrate (N_methyl_GABA) [11]. Mouse knockouts of SLC6A13 are known to have 50% lower taurine levels in the liver compared to wildtype individuals [12].…”

Section: Resultsmentioning

confidence: 99%

Understanding the liver under heat stress with statistical learning: an integrated metabolomics and transcriptomics computational approach

et al. 2019

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Background We present results from a computational analysis developed to integrate transcriptome and metabolomic data in order to explore the heat stress response in the liver of the modern broiler chicken. Heat stress is a significant cause of productivity loss in the poultry industry, both in terms of increased livestock morbidity and its negative influence on average feed efficiency. This study focuses on the liver because it is an important regulator of metabolism, controlling many of the physiological processes impacted by prolonged heat stress. Using statistical learning methods, we identify genes and metabolites that may regulate the heat stress response in the liver and adaptations required to acclimate to prolonged heat stress. Results We describe how disparate systems such as sugar, lipid and amino acid metabolism, are coordinated during the heat stress response. Conclusions Our findings provide more detailed context for genomic studies and generates hypotheses about dietary interventions that can mitigate the negative influence of heat stress on the poultry industry. Electronic supplementary material The online version of this article (10.1186/s12864-019-5823-x) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Understanding the liver under heat stress with statistical learning: an integrated metabolomics and transcriptomics computational approach

et al. 2019

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“…Acetic acid is a short-chain fatty acid, which is involved in the synthesis of cholesterol. Other metabolites such as N-acetyl-l-aspartic acid, glutamate and hypotaurine are very good antioxidants 37,38 .…”

Section: Discussionmentioning

confidence: 99%

Toxicology of paraquat and pharmacology of the protective effect of 5-hydroxy-1-methylhydantoin on lung injury caused by paraquat based on metabolomics

Gao

Yuan

et al. 2020

Sci Rep

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Paraquat (PQ) is a non-selective herbicide and is exceedingly toxic to humans. The mechanism of PQ toxicity is very complex and has not been clearly defined. There is no specific antidote for PQ poisoning. 5-hydroxy-1-methylhydantoin (HMH) is an intrinsic antioxidant and can protect against renal damage caused by PQ. The mechanism of PQ toxicology and the possible effects of HMH on PQ-induced lung injury were determined in this study. It was found that PQ decreased superoxide dismutase (SOD) activity and elevated the level of malondialdehyde (MDA), while HMH elevated SOD activity and decreased the level of MDA. Based on metabolomics, the citrate cycle, glutathione metabolism, taurine and hypotaurine metabolism, regulation of lipolysis in adipocytes, inflammatory mediator regulation of tRp channels, purine and pyrimidine metabolism, aldosterone synthesis and secretion, and phenylalanine metabolism were changed in the PQ group. Compared with the PQ group, the levels of N-acetyl-l-aspartic acid, L-glutamic acid, L-aspartic acid, mesaconic acid, adenosine 5′ monophosphate, methylmalonic acid, cytidine, phosphonoacetic acid, hypotaurine, glutathione (reduced) and cysteinylglycine increased, while the levels of corticosterone, xanthine, citric acid, prostaglandin G2, 4-pyridoxic acid and succinyl proline decreased in the HMH group. These metabolites revealed that HMH can alleviate inflammation caused by PQ and elevate the activity of intrinsic antioxidants. In conclusion, our results revealed PQ toxicology and the pharmacology underlying the protective effect of HMH on lung injury due to PQ. Toxicity caused by PQ results in lipid peroxidation and an increase in reactive oxygen species (RoS), nitric oxide (no), damage to the biliary system, gastrointestinal system and nervous system, in addition to lungs, kidneys, and the liver. HMH is a good antioxidant and protects against lung injury caused by PQ. In summary, HMH efficiently reduced PQ-induced lung injury in mice. Paraquat (PQ, 1,1′-dimethyl-4-4′-bipyridinium dichloride) is a highly toxic quaternary ammonium herbicide widely used in agriculture. The mortality rate of PQ poisoning is as high as 60-80%, mainly due to acute lung injury and progressive pulmonary fibrosis 1-3. Moreover, there is no specific antidote for PQ poisoning. Following PQ poisoning, the lungs are the main target organs, and the redox reaction occurs after the uptake of PQ in the lungs, which interferes with mitochondrial electron transfer, generates a large number of oxygen free radicals, and induces lipid peroxidation injury 2. PQ enters the body and is excreted in the form of a prototype in the kidney, where the concentration is highest, resulting in impaired renal function. PQ cannot be excreted normally and further accumulates in the body; thus, involving other organs such as the liver, heart and lung, resulting in multiple organ failure 2. Creatinine is a degradation product of creatine, which is degraded at a constant rate. When renal function is impaired, large amounts of creatinine are acc...

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“…As a taurine precursor, hypotaurine is produced by cysteine. At high-LIN treatment groups, genes cysteine dioxygenase (cdo) and cysteamine dioxygenase (ado) involved in two ways of producing cysteine were both downregulated [55]. Besides, hypotaurine is an endogenous antioxidant, the decrease of these two genes ado and cdo1 suggested a reduction of intracellular hypotaurine level, which is proof of cellular responses to oxidative stress [56].…”

Section: Genes Involved In Amino Acids Nucleotide and Carbohydrate mentioning

confidence: 98%

Lincomycin-Induced Transcriptional Alterations in the Green Alga Raphidocelis subcapitata

et al. 2020

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Lincomycin (LIN), as a waterborne contaminant, may pose a threat to algal health and may affect the provision of ecosystem services. In addition, the molecular mechanisms of lincomycin in algae are still unknown. Here, we attempted to use the transcriptome analysis to elucidate for the first time the potential impact of LIN at an environmentally relevant concentration on the algal growth, and verify the hypothesis that lincomycin can disrupt algal protein synthesis by combining with its subunits of ribosome at high-LIN level. In this study, 7-day growth inhibition tests and RNA-seq sequencing were conducted in Raphidocelis subcapitata (R. subcapitata) in response to a LIN at the concentrations of 0.5 µg L−1 (low), 5 µg L−1 (medium), and 400 µg L−1 (high) treatment groups. A negligible influence on algal growth and merely 21 (21 up- and 0 downregulated) differentially expressed genes (DEGs) was observed at low concentration of LIN, and medium groups showed a 13.4% inhibition and 92 (64 up- and 48 downregulated) DEGs, while high-LIN dosing caused 65.4% reduction in algal growth and 2514 (663 up- and 1851 downregulated) DEGs. In 0.5 and 5 µg L−1 groups, LIN upregulated the genes in the process of photosynthesis consisting of photosynthesis-antenna proteins, and porphyrin and chlorophyll metabolism pathways, suggesting that photosynthesis at low LIN exposure was more sensitive than algal growth. Whereas DEGs in the 400 µg L−1 group were mostly enriched in carbohydrate, carbon fixation in photosynthetic organisms, and nucleotide metabolism pathways. Furthermore, genes involved in detoxification processes were nearly downregulated in high-LIN group. In addition, genes encoding the antioxidant enzymes in the peroxisome pathway such as superoxide dismutase (sod2), peroxin-2 (pex2), 2,4-dienoyl-CoA reductase ((3E)-enoyl-CoA-producing) (decr2) were upregulated, which are responsible for deleting extra intracellular reactive oxygen species (ROS) caused by LIN to protect algal health, suggesting the occurrence of oxidative stress. Taken together, this is the first meticulous study unraveling the molecular mechanism of antibiotics in algae.

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Hypotaurine Is a Substrate of GABA Transporter Family Members GAT2/Slc6a13 and TAUT/Slc6a6

Cited by 14 publications

References 35 publications

Understanding the liver under heat stress with statistical learning: an integrated metabolomics and transcriptomics computational approach

Understanding the liver under heat stress with statistical learning: an integrated metabolomics and transcriptomics computational approach

Toxicology of paraquat and pharmacology of the protective effect of 5-hydroxy-1-methylhydantoin on lung injury caused by paraquat based on metabolomics

Lincomycin-Induced Transcriptional Alterations in the Green Alga Raphidocelis subcapitata

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