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Author Noriyuki Akahoshi

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Increased Urinary 3-Mercaptolactate Excretion and Enhanced Passive Systemic Anaphylaxis in Mice Lacking Mercaptopyruvate Sulfurtransferase, a Model of Mercaptolactate-Cysteine Disulfiduria.

Noriyuki Akahoshi, Tatsuro Minakawa, Masashi Miyashita, Uran Sugiyama, Chihiro Saito, Rintaro Takemoto, Akihiro Honda, Waka Kamichatani, Shotaro Kamata, Yasumi Anan, Isao Ishii,

Mercaptopyruvate sulfurtransferase (Mpst) and its homolog thiosulfate sulfurtransferase (Tst = rhodanese) detoxify cyanide to thiocyanate. Mpst is attracting attention as one of the four endogenous hydrogen sulfide (H2S)/reactive sulfur species (RSS)-producing enzymes, along with cystathionine β-synthase (Cbs), cystathionine γ-lyase (Cth), and cysteinyl-tRNA synthetase 2 (Cars2). MPST deficiency was found in ... Read more >>

Int J Mol Sci (International journal of molecular sciences)
[2020, 21(3):]

Cited: 0 times

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Lysophosphatidic acid-induced YAP/TAZ activation promotes developmental angiogenesis by repressing Notch ligand Dll4.

Daisuke Yasuda, Daiki Kobayashi, Noriyuki Akahoshi, Takayo Ohto-Nakanishi, Kazuaki Yoshioka, Yoh Takuwa, Seiya Mizuno, Satoru Takahashi, Satoshi Ishii,

Lysophosphatidic acid (LPA) is a potent lipid mediator with various biological functions mediated through six G protein-coupled receptors (GPCRs), LPA1-6. Previous studies have demonstrated that LPA-Gα12/Gα13 signaling plays an important role in embryonic vascular development. However, the responsible LPA receptors and underlying mechanisms are poorly understood. Here, we show a ... Read more >>

J. Clin. Invest. (The Journal of clinical investigation)
[2019, 129(10):4332-4349]

Cited: 1 time

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Preeclampsia-Like Features and Partial Lactation Failure in Mice Lacking Cystathionine γ-Lyase-An Animal Model of Cystathioninuria.

Noriyuki Akahoshi, Hiroki Handa, Rintaro Takemoto, Shotaro Kamata, Masahide Yoshida, Tatsushi Onaka, Isao Ishii,

Elevated plasma homocysteine levels are considered as a risk factor for cardiovascular diseases as well as preeclampsia-a pregnancy disorder characterized by hypertension and proteinuria. We previously generated mice lacking cystathionine γ-lyase (Cth) as cystathioninuria models and found them to be with cystathioninemia/homocysteinemia. We investigated whether Cth-deficient (Cth-/-) pregnant mice display ... Read more >>

Int J Mol Sci (International journal of molecular sciences)
[2019, 20(14):]

Cited: 0 times

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Dietary selenium deficiency or selenomethionine excess drastically alters organ selenium contents without altering the expression of most selenoproteins in mice.

Noriyuki Akahoshi, Yasumi Anan, Yuri Hashimoto, Natsumi Tokoro, Ryoka Mizuno, Seiya Hayashi, Shingo Yamamoto, Ki-Ichi Shimada, Shotaro Kamata, Isao Ishii,

Selenium is an essential trace element, and its deficiency can cause cardiomyopathy, arrhythmias and increased susceptibility to infection. Such clinical symptoms are considered primarily attributed to decreased expression of some of the 25 selenocysteine-containing selenoproteins in humans. Conversely, a selenium-excessive diet can cause acute poisoning and chronic symptoms with unknown ... Read more >>

J. Nutr. Biochem. (The Journal of nutritional biochemistry)
[2019, 69:120-129]

Cited: 0 times

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Abnormal Amino Acid Profiles of Blood and Cerebrospinal Fluid from Cystathionine β-Synthase-Deficient Mice, an Animal Model of Homocystinuria.

Noriyuki Akahoshi, Akira Yokoyama, Tomoko Nagata, Asumi Miura, Shotaro Kamata, Isao Ishii,

Mental retardation is the most common feature among inborn errors of amino acid metabolism. Patients with homocystinuria/homocysteinemia caused by cystathionine β-synthase (CBS) deficiency suffer from thromboembolism and mental retardation from early ages; therefore, detection by newborn screening is performed. Furthermore, elevated levels of serum homocysteine during pregnancy are associated with ... Read more >>

Biol. Pharm. Bull. (Biological & pharmaceutical bulletin)
[2019, 42(6):1054-1057]

Cited: 1 time

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The Gα12/13-coupled receptor LPA4 limits proper adipose tissue expansion and remodeling in diet-induced obesity.

Keisuke Yanagida, Hidemitsu Igarashi, Daisuke Yasuda, Daiki Kobayashi, Takayo Ohto-Nakanishi, Noriyuki Akahoshi, Atsushi Sekiba, Tsudoi Toyoda, Tomoko Ishijima, Yuji Nakai, Nobuhiro Shojima, Naoto Kubota, Keiko Abe, Takashi Kadowaki, Satoshi Ishii, Takao Shimizu,

White adipose tissue (WAT) can dynamically expand and remodel through adipocyte hypertrophy and hyperplasia. The relative contribution of these 2 mechanisms to WAT expansion is a critical determinant of WAT function and dysfunction in obesity. However, little is known about the signaling systems that determine the mechanisms of WAT expansion. ... Read more >>

JCI Insight (JCI insight)
[2018, 3(24):]

Cited: 2 times

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Mutations in Homocysteine Metabolism Genes Increase Keratin N-Homocysteinylation and Damage in Mice.

Kamila Borowczyk, Jacek Wróblewski, Joanna Suliburska, Noriyuki Akahoshi, Isao Ishii, Hieronim Jakubowski,

Genetic or nutritional deficiencies in homocysteine (Hcy) metabolism increase Hcy-thiolactone, which causes protein damage by forming isopetide bonds with lysine residues, generating N-Hcy-protein. In the present work, we studied the prevalence and genetic determinants of keratin damage caused by homocysteinylation. We found that in mammals and birds, 35 to 98% ... Read more >>

Int J Genomics (International journal of genomics)
[2018, 2018:7570850]

Cited: 0 times

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LPA5 signaling is involved in multiple sclerosis-mediated neuropathic pain in the cuprizone mouse model.

Ryoko Tsukahara, Shinji Yamamoto, Keisuke Yoshikawa, Mari Gotoh, Tamotsu Tsukahara, Hiroyuki Neyama, Satoshi Ishii, Noriyuki Akahoshi, Keisuke Yanagida, Hayakazu Sumida, Masatake Araki, Kimi Araki, Ken-Ichi Yamamura, Kimiko Murakami-Murofushi, Hiroshi Ueda,

Lysophosphatidic acid (LPA) and LPA1 receptor signaling play a crucial role in the initiation of peripheral nerve injury-induced neuropathic pain through the alternation of pain-related genes/proteins expression and demyelination. However, LPA and its signaling in the brain are still poorly understood. In the present study, we revealed that the LPA5 ... Read more >>

J. Pharmacol. Sci. (Journal of pharmacological sciences)
[2018, 136(2):93-96]

Cited: 2 times

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Cystathionine γ-Lyase-Produced Hydrogen Sulfide Controls Endothelial NO Bioavailability and Blood Pressure.

István András Szijártó, Lajos Markó, Milos R Filipovic, Jan Lj Miljkovic, Christoph Tabeling, Dmitry Tsvetkov, Ning Wang, Luiza A Rabelo, Martin Witzenrath, André Diedrich, Jens Tank, Noriyuki Akahoshi, Shotaro Kamata, Isao Ishii, Maik Gollasch,

Hydrogen sulfide (H2S) and NO are important gasotransmitters, but how endogenous H2S affects the circulatory system has remained incompletely understood. Here, we show that CTH or CSE (cystathionine γ-lyase)-produced H2S scavenges vascular NO and controls its endogenous levels in peripheral arteries, which contribute to blood pressure regulation. Furthermore, eNOS (endothelial ... Read more >>

Hypertension (Hypertension (Dallas, Tex. : 1979))
[2018, 71(6):1210-1217]

Cited: 7 times

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Lysophosphatidic acid receptors LPA4 and LPA6 differentially promote lymphocyte transmigration across high endothelial venules in lymph nodes.

Erina Hata, Naoko Sasaki, Akira Takeda, Kazuo Tohya, Eiji Umemoto, Noriyuki Akahoshi, Satoshi Ishii, Kana Bando, Takaya Abe, Kuniyuki Kano, Junken Aoki, Haruko Hayasaka, Masayuki Miyasaka,

Naive lymphocytes continuously migrate from the blood into lymph nodes (LNs) via high endothelial venules (HEVs). To extravasate from the HEVs, lymphocytes undergo multiple adhesion steps, including tethering, rolling, firm adhesion and transmigration. We previously showed that autotaxin (ATX), an enzyme that generates lysophosphatidic acid (LPA), is highly expressed in ... Read more >>

Int. Immunol. (International immunology)
[2016, 28(6):283-292]

Cited: 5 times

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2D DIGE proteomic analysis highlights delayed postnatal repression of α-fetoprotein expression in homocystinuria model mice.

Shotaro Kamata, Noriyuki Akahoshi, Isao Ishii,

Cystathionine β-synthase-deficient (Cbs (-/-)) mice, an animal model for homocystinuria, exhibit hepatic steatosis and juvenile semilethality via as yet unknown mechanisms. The plasma protein profile of Cbs (-/-) mice was investigated by proteomic analysis using two-dimensional difference gel electrophoresis and matrix-assisted laser desorption/ionization-time of flight/mass spectrometry. We found hyperaccumulation of ... Read more >>

FEBS Open Bio (FEBS open bio)
[2015, 5:535-541]

Cited: 1 time

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The lysophosphatidic acid receptor LPA4 regulates hematopoiesis-supporting activity of bone marrow stromal cells.

Hidemitsu Igarashi, Noriyuki Akahoshi, Takayo Ohto-Nakanishi, Daisuke Yasuda, Satoshi Ishii,

Lysophosphatidic acid (LPA) is a pleiotropic lipid mediator that acts through G protein-coupled receptors (LPA1-6). Although several biological roles of LPA4 are becoming apparent, its role in hematopoiesis has remained unknown. Here, we show a novel regulatory role for LPA4 in hematopoiesis. Lpar4 mRNA was predominantly expressed in mouse bone marrow ... Read more >>

Sci Rep (Scientific reports)
[2015, 5:11410]

Cited: 3 times

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Hemizygosity of transsulfuration genes confers increased vulnerability against acetaminophen-induced hepatotoxicity in mice.

Yoshifumi Hagiya, Shotaro Kamata, Saya Mitsuoka, Norihiko Okada, Saori Yoshida, Junya Yamamoto, Rika Ohkubo, Yumi Abiko, Hidenori Yamada, Noriyuki Akahoshi, Tadashi Kasahara, Yoshito Kumagai, Isao Ishii,

The key mechanism for acetaminophen hepatotoxicity is cytochrome P450 (CYP)-dependent formation of N-acetyl-p-benzoquinone imine, a potent electrophile that forms protein adducts. Previous studies revealed the fundamental role of glutathione, which binds to and detoxifies N-acetyl-p-benzoquinone imine. Glutathione is synthesized from cysteine in the liver, and N-acetylcysteine is used as a ... Read more >>

Toxicol. Appl. Pharmacol. (Toxicology and applied pharmacology)
[2015, 282(2):195-206]

Cited: 8 times

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Hyperhomocysteinemia abrogates fasting-induced cardioprotection against ischemia/reperfusion by limiting bioavailability of hydrogen sulfide anions.

Shintaro Nakano, Isao Ishii, Ken Shinmura, Kayoko Tamaki, Takako Hishiki, Noriyuki Akahoshi, Tomoaki Ida, Tsuyoshi Nakanishi, Shotaro Kamata, Yoshito Kumagai, Takaaki Akaike, Keiichi Fukuda, Motoaki Sano, Makoto Suematsu,

Elevated plasma homocysteine levels are considered an independent risk factor for cardiovascular diseases. Experimental evidence has shown that hydrogen sulfide anion (HS(-)) protects the myocardium from ischemia/reperfusion (IR) injury. Both homocysteine levels and endogenous HS(-) production are mainly regulated by two transsulfuration enzymes, cystathionine β-synthase (CBS) and cystathionine γ-lyase (CTH). ... Read more >>

J. Mol. Med. (Journal of molecular medicine (Berlin, Germany))
[2015, 93(8):879-889]

Cited: 16 times

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Neutral aminoaciduria in cystathionine β-synthase-deficient mice; an animal model of homocystinuria.

Noriyuki Akahoshi, Shotaro Kamata, Masashi Kubota, Takako Hishiki, Yoshiko Nagahata, Tomomi Matsuura, Chiho Yamazaki, Yuka Yoshida, Hidenori Yamada, Yasuki Ishizaki, Makoto Suematsu, Tadashi Kasahara, Isao Ishii,

The kidney is one of the major loci for the expression of cystathionine β-synthase (CBS) and cystathionine γ-lyase (CTH). While CBS-deficient (Cbs(-/-)) mice display homocysteinemia/methioninemia and severe growth retardation, and rarely survive beyond the first 4 wk, CTH-deficient (Cth(-/-)) mice show homocysteinemia/cystathioninemia but develop with no apparent abnormality. This study ... Read more >>

Am. J. Physiol. Renal Physiol. (American journal of physiology. Renal physiology)
[2014, 306(12):F1462-76]

Cited: 6 times

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TDAG8 activation inhibits osteoclastic bone resorption.

Hisako Hikiji, Daisuke Endo, Kyoji Horie, Takeshi Harayama, Noriyuki Akahoshi, Hidemitsu Igarashi, Yasuyuki Kihara, Keisuke Yanagida, Junji Takeda, Takehiko Koji, Takao Shimizu, Satoshi Ishii,

Although the roles of acids in bone metabolism are well characterized, the function of proton-sensing receptors in bone metabolism remains to be explored. In this study, we evaluated the role of proton-sensing receptor T-cell death-associated gene 8 (TDAG8) in osteoclastic activity during bone loss after ovariectomy. Through observations of bone ... Read more >>

FASEB J. (FASEB journal : official publication of the Federation of American Societies for Experimental Biology)
[2014, 28(2):871-879]

Cited: 13 times

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Methionine excess in diet induces acute lethal hepatitis in mice lacking cystathionine γ-lyase, an animal model of cystathioninuria.

Hidenori Yamada, Noriyuki Akahoshi, Shotaro Kamata, Yoshifumi Hagiya, Takako Hishiki, Yoshiko Nagahata, Tomomi Matsuura, Naoharu Takano, Masatomo Mori, Yasuki Ishizaki, Takashi Izumi, Yoshito Kumagai, Tadashi Kasahara, Makoto Suematsu, Isao Ishii,

Physiological roles of the transsulfuration pathway have been recognized by its contribution to the synthesis of cytoprotective cysteine metabolites, such as glutathione, taurine/hypotaurine, and hydrogen sulfide (H(2)S), whereas its roles in protecting against methionine toxicity remained to be clarified. This study aimed at revealing these roles by analyzing high-methionine diet-fed ... Read more >>

Free Radic. Biol. Med. (Free radical biology & medicine)
[2012, 52(9):1716-1726]

Cited: 31 times

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TOF-SIMS imaging of halide/thiocyanate anions and hydrogen sulfide in mouse kidney sections using silver-deposited plates.

Noriyuki Akahoshi, Itsuko Ishizaki, Masayuki Naya, Toshihiko Maekawa, Shougo Yamazoe, Tadashi Horiuchi, Mayumi Kajimura, Yoshiharu Ohashi, Makoto Suematsu, Isao Ishii,

In vivo imaging of reactive small molecule metabolites with high spatial resolution and specificity could give clues to understanding pathophysiology of various diseases. We herein applied time of flight-secondary ion mass spectrometry (TOF-SIMS) to newly developed silver-deposited plates that were stamped on mouse tissues, and succeeded in visualization of halide ... Read more >>

Anal Bioanal Chem (Analytical and bioanalytical chemistry)
[2012, 402(5):1859-1864]

Cited: 3 times

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Frequent spontaneous seizures followed by spatial working memory/anxiety deficits in mice lacking sphingosine 1-phosphate receptor 2.

Noriyuki Akahoshi, Yasuki Ishizaki, Hiroki Yasuda, Yoshiya L Murashima, Toshikazu Shinba, Kaoru Goto, Toshiyuki Himi, Jerold Chun, Isao Ishii,

The diverse physiological effects of sphingosine 1-phosphate (S1P) are mostly mediated by its five cognate G protein-coupled receptors, S1P(1)-S1P(5), which have attracted much attention as future drug targets. To gain insight into S1P(2)-mediated signaling, we analyzed frequent spontaneous seizures in S1P(2)-deficient (S1P(2)(-/-)) mice obtained after several backcrosses onto a C57BL/6N ... Read more >>

Epilepsy Behav (Epilepsy & behavior : E&B)
[2011, 22(4):659-665]

Cited: 16 times

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Triacylglycerol/phospholipid molecular species profiling of fatty livers and regenerated non-fatty livers in cystathionine beta-synthase-deficient mice, an animal model for homocysteinemia/homocystinuria.

Kazutaka Ikeda, Akiko Kubo, Noriyuki Akahoshi, Hidenori Yamada, Naoya Miura, Takako Hishiki, Yoshiko Nagahata, Tomomi Matsuura, Makoto Suematsu, Ryo Taguchi, Isao Ishii,

Fatty liver is one of the typical manifestations in homocysteinemia/homocystinuria patients and their genetic animal model, mice lacking cystathionine β-synthase (Cbs(-/-)). The vast majority of Cbs(-/-) die within 4 weeks after birth via yet unknown mechanisms, whereas a small portion survive to adulthood, escaping fatty degeneration of the liver during ... Read more >>

Anal Bioanal Chem (Analytical and bioanalytical chemistry)
[2011, 400(7):1853-1863]

Cited: 14 times

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Cystathionine gamma-Lyase-deficient mice require dietary cysteine to protect against acute lethal myopathy and oxidative injury.

Isao Ishii, Noriyuki Akahoshi, Hidenori Yamada, Shintaro Nakano, Takashi Izumi, Makoto Suematsu,

Cysteine is considered a nonessential amino acid in mammals as it is synthesized from methionine via trans-sulfuration. However, premature infants or patients with hepatic failure may require dietary cysteine due to a lack of cystathionine gamma-lyase (CTH), a key trans-sulfuration enzyme. Here, we generated CTH-deficient (Cth(-/-)) mice as an animal ... Read more >>

J. Biol. Chem. (The Journal of biological chemistry)
[2010, 285(34):26358-26368]

Cited: 110 times

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Genetic background conversion ameliorates semi-lethality and permits behavioral analyses in cystathionine beta-synthase-deficient mice, an animal model for hyperhomocysteinemia.

Noriyuki Akahoshi, Chiho Kobayashi, Yasuki Ishizaki, Takashi Izumi, Toshiyuki Himi, Makoto Suematsu, Isao Ishii,

Cystathionine beta-synthase-deficient mice (Cbs(-/-)) exhibit several pathophysiological features similar to hyperhomocysteinemic patients, including endothelial dysfunction and hepatic steatosis. Heterozygous mutants (Cbs(+/-)) on the C57BL/6J background are extensively analyzed in laboratories worldwide; however, detailed analyses of Cbs(-/-) have been hampered by the fact that they rarely survive past the weaning age ... Read more >>

Hum. Mol. Genet. (Human molecular genetics)
[2008, 17(13):1994-2005]

Cited: 29 times

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Increased expression of the lysosomal protease cathepsin S in hippocampal microglia following kainate-induced seizures.

Noriyuki Akahoshi, Yoshiya L Murashima, Toshiyuki Himi, Yasuki Ishizaki, Isao Ishii,

To examine lesions caused by seizures in the developing brain, seizures were induced by the intraperitoneal injection of kainate and nicotine into juvenile mice. After a week, whole brain sections were examined using histochemistry and the gene expression profiles in the neocortices and hippocampi were analyzed using a DNA microarray. ... Read more >>

Neurosci. Lett. (Neuroscience letters)
[2007, 429(2-3):136-141]

Cited: 13 times

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Differential induction of cystathionine gamma-lyase in the livers and kidneys of mouse dams during gestation and lactation.

Noriyuki Akahoshi, Takashi Izumi, Yasuki Ishizaki, Isao Ishii,

Cystathionine gamma-lyase (CSE) is the last key enzyme in the transsulfuration pathway for the biosynthesis of cysteine from methionine in mammals, and catalyzes the hydrolysis of cystathionine into cysteine. Cysteine can be provided through diet; however, several investigators have suggested that infants may require dietary supplements of cysteine because of ... Read more >>

Biol. Pharm. Bull. (Biological & pharmaceutical bulletin)
[2006, 29(9):1799-1802]

Cited: 10 times

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Murine cystathionine gamma-lyase: complete cDNA and genomic sequences, promoter activity, tissue distribution and developmental expression.

Isao Ishii, Noriyuki Akahoshi, Xiao-Nian Yu, Yuriko Kobayashi, Kazuhiko Namekata, Gen Komaki, Hideo Kimura,

Cystathionine gamma-lyase (CSE) is the last key enzyme in the trans-sulphuration pathway for biosynthesis of cysteine from methionine. Cysteine could be provided through diet; however, CSE has been shown to be important for the adequate supply of cysteine to synthesize glutathione, a major intracellular antioxidant. With a view to determining ... Read more >>

Biochem. J. (The Biochemical journal)
[2004, 381(Pt 1):113-123]

Cited: 148 times

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