Papers - OHTAKE Kazuo
-
Oral nitrite ameliorates dextran sulfate sodium-induced acute experimental colitis in mice. Reviewed International journal
Ohtake K, Koga M, Uchida H, Sonoda K, Ito J, Uchida M, Natsume H, Kobayashi J
Nitric oxide : biology and chemistry 23 ( 1 ) 65 - 73 2010.08
Authorship：Lead author Language：English Publishing type：Research paper (scientific journal)
Inflammatory bowel diseases (IBDs) such as Crohn's disease and ulcerative colitis are chronic inflammatory disorders of the intestinal tract with excessive production of cytokines, adhesion molecules, and reactive oxygen species. Although nitric oxide (NO) is reported to be involved in the onset and progression of IBDs, it remains controversial as to whether NO is toxic or protective in experimental colitis. We investigated the effects of oral nitrite as a NO donor on dextran sulfate sodium (DSS)-induced acute colitis in mice. Mice were fed DSS in their drinking water with or without nitrite for up to 7days. The severity of colitis was assessed by disease activity index (DAI) observed over the experimental period, as well as by the other parameters, including colon lengths, hematocrit levels, and histological scores at day 7. DSS treatment induced severe colitis by day 7 with exacerbation in DAI and histological scores. We first observed a significant decrease in colonic nitrite levels and increase in colonic TNF-alpha expression at day 3 after DSS treatment, followed by increased colonic myeloperoxidase (MPO) activity and increased colonic expressions of both inducible NO synthase (iNOS) and heme oxygenase-1 (HO-1) at day 7. Oral nitrite supplementation to colitis mice reversed colonic nitrite levels and TNF-alpha expression to that of normal control mice at day 3, resulting in the reduction of MPO activity as well as iNOS and HO-1 expressions in colonic tissues with clinical and histological improvements at day 7. These results suggest that oral nitrite inhibits inflammatory process of DSS-induced experimental colitis by supplying nitrite-derived NO instead of impaired colonic NOS activity.
-
Proteomic approach for identification of protein S-nitrosation in mouse gastric mucosa treated with S-nitrosoglutathione. Reviewed International journal
Kazuo Ohtake, Norihisa Shimada, Hiroyuki Uchida, Jun Kobayashi
Journal of proteomics 72 ( 5 ) 750 - 60 2009.07
Authorship：Lead author Language：English Publishing type：Research paper (scientific journal)
Nitric oxide, endogenously generated and exogenously supplied to the stomach, plays an important role in gastric physiological and pathological processes, including epithelial secretion, barrier function, immune response, and carcinogenesis. One of the mechanisms by which NO and related nitroso-compounds transmit their signals is S-nitrosation-mediated protein modification. To screen and identify gastric mucosal proteins that are uniquely sensitive to S-nitrosation, we reacted mouse gastric mucosal lysates with S-nitrosoglutathione, a physiologically relevant nitrosating agent, then performed proteomic analysis including the biotin-switch assay. The results showed that more than sixty protein spots on 2-DE were detected, and thirty-two of these were identified by MALDI-TOF MS and PMF. Eight of these identified proteins were unique S-nitrosated proteins not previously reported. Using Western blot technique, we further confirmed S-nitrosation especially in four proteins such as carbonic anhydrase-2, nucleoside diphosphate kinase B, Raf kinase inhibitor protein, and galectin-2, all known to be closely related to gastric mucosal protection and integrity, cell migration, and tumor metastasis. In addition, ex vivo study closer to in vivo situation also demonstrated these four proteins significantly S-nitrosated with S-nitrosoglutathione in mouse gastric mucosa. These findings will provide useful information regarding the linkage of protein S-nitrosation to gastric physiology and pathophysiology.
-
Dietary nitrite inhibits early glomerular injury in streptozotocin-induced diabetic nephropathy in rats. Reviewed International journal
Kazuo Ohtake, Yuichi Ishiyama, Hiroyuki Uchida, Etsuko Muraki, Jun Kobayashi
Nitric oxide : biology and chemistry 17 ( 2 ) 75 - 81 2007.09
Authorship：Lead author Language：English Publishing type：Research paper (scientific journal)
Increased production of reactive oxygen species (ROS) is a key event leading to microvascular complications, including nephropathy, in diabetes mellitus (DM). Excessive ROS and oxidative stress in DM have been reported to be associated with subsequent impaired nitric oxide (NO) bioavailability. The aim of this study is to examine the beneficial function of dietary nitrite supplementation as an interventional NO donor to attenuate early progression of diabetic nephropathy. To test this hypothesis, male Sprague-Dawley rats were randomly divided into four groups: non-diabetic rats given water with or without nitrite (nitrite-treated or untreated, respectively), and streptozotocin-induced diabetic rats given water with or without nitrite (nitrite-treated or untreated, respectively). After a 4 week experimental period, untreated diabetic rats exhibited significantly higher malondialdehyde (MDA) levels in the kidney compared with untreated non-diabetic rats, accompanied by a reduction in levels of endogenous NO synthase-derived nitrite. However, dietary nitrite supplementation to diabetic rats not only decreased MDA levels but also increased nitrite levels in the kidney to the same levels as in the non-diabetic kidney. These improvements accompanied an improvement in the parameters of glomerular injury, including urinary protein and albumin excretion, histopathological glomerular hypertrophy, and mesangial matrix accumulation. These results indicate that dietary nitrite is effective in the prevention of early diabetic glomerular injury in which NO bioavailability is impaired.
-
Poly-L-arginine enhances paracellular permeability via serine/threonine phosphorylation of ZO-1 and tyrosine dephosphorylation of occludin in rabbit nasal epithelium. Reviewed International journal
Kazuo Ohtake, Takuya Maeno, Hideo Ueda, Masahiko Ogihara, Hideshi Natsume, Yasunori Morimoto
Pharmaceutical research 20 ( 11 ) 1838 - 45 2003.11
Authorship：Lead author Language：English Publishing type：Research paper (scientific journal)
PURPOSE: The purpose of the present study is to explore whether a poly-L-arginine (poly-L-Arg)-induced increase in tight junctions (TJ) permeability of fluorescein isothiocyanate-labeled dextran (MW 4.4 kDa, FD-4) is associated with the Ca2+-dependent signaling and occurs following the phosphorylation/dephosphorylation of TJ proteins. METHODS: Excised rabbit nasal epithelium was mounted in an Ussing-type chamber for measurement of FD-4 transport and membrane conductance (Gt) in the presence of various inhibitors that are involved in the Ca2+-dependent pathway and the phosphorylation/dephosphorylation of TJ proteins. The resultant distribution of TJ proteins was observed using confocal laser scanning microscopy (CLSM) in an immunostaining. RESULTS: The increase in TJ permeability of FD4 induced by 0.2 mg/ml poly-L-Arg was not altered by treatment with inhibitors (of possible Ca2+ mobilization pathways followed by exposure of poly-L-Arg, suggesting that the promoting effect of poly-L-Arg is independent of Ca2+-related signaling. On the other hand, the protein kinase C (PKC) and tyrosine phosphatase inhibitors suppress the increase in TJ permeability by poly-L-Arg, indicating that serine/threonine phosphorylation by way of Ca2+-independent PKC and tyrosine dephosphorylation of junction proteins may have occurred. Furthermore, immunofluorescent monitoring of ZO-1, a TJ associated protein, and occludin, an integral membrane protein localizing at TJ, after preincubation with PKC and tyrosine phosphatase inhibitors followed by poly-L-Arg treatment has shown that the internalization of ZO-1 and occludin occurred by way of serine/threonine phosphorylation by PKC activation and by way of tyrosine dephosphorylation, respectively, providing TJ disassembly. CONCLUSIONS: We conclude that poly-L-Arg enhances the paracellular permeability of FD-4 (i.e., macromolecules), at least, by way of both serine/threonine phosphorylation of ZO-1 and tyrosine dephosphorylation of occludin in rabbit nasal epithelium.
-
Poly-L-arginine predominantly increases the paracellular permeability of hydrophilic macromolecules across rabbit nasal epithelium in vitro. Reviewed International journal
Kazuo Ohtake, Takaya Maeno, Hideo Ueda, Hideshi Natsume, Yasunori Morimoto
Pharmaceutical research 20 ( 2 ) 153 - 60 2003.02
Authorship：Lead author Language：English Publishing type：Research paper (scientific journal)
PURPOSE: The purpose of this work was to characterize the main transport pathway of hydrophilic macromolecules induced by poly-L-arginine (poly-L-Arg; molecular weight 42.4 kDa) across the excised rabbit nasal epithelium. METHODS: Excised rabbit nasal epithelium was mounted in an Ussing-type chamber for measurement of fluorescein isothiocyanate-labeled dextran (FD-4; molecular weight 4.4 kDa) transport and transepithelial electrical resistance (TEER). The main transport pathway of FD-4 enhanced by poly-L-Arg was evaluated using confocal laser scanning microscopy. Immunolocalization of junction proteins (ZO-1, occludin, and E-cadherin) after treatment with poly-L-Arg was also observed. RESULTS: After apical application of a poly-L-Arg (0.05, 0.5, and 5 mg/mL), the permeability coefficient of FD-4 increased by 1.6-, 2.9-, and 5.2-fold, respectively, compared with the control of 5.2 +/- 1.3 x 10(-7) cm/s. Consistent with the increase in transport, there was a concurrent reduction in TEER. At a concentration of 0.05 mg/mL poly-L-Arg. both FD-4 transport and TEER returned to the control level. A good correlation was obtained between the FD-4 permeability coefficient and 1/TEER. Basolateral application of poly-L-Arg at 5 mg/mL, however, did not increase FD-4 transport. Marked FD-4 fluorescence was located in the paracellular spaces after treatment with apical poly-L-Arg compared with that in the absence of poly-L-Arg. Immunofluorescence of ZO-1, occludin, and E-cadherin in cell-to-cell junctions was reduced and distributed into the cytoplasm by apical application of poly-L-Arg, suggesting that poly-L-Arg regulates the junction proteins to enhance paracellular permeability across the nasal epithelium. After pretreatment with either 2,4-dinitrophenol or ouabain, the enhancing effect of apical poly-L-Arg was abolished, indicating the contribution of metabolic energy (cell viability) to the poly-L-Arg-mediated enhancing effect. CONCLUSION: In the nasal epithelium, apical poly-L-Arg appears to increase predominantly the paracellular transport of hydrophilic macromolecules via disorganization of tight- and adherens-junction proteins. The regulatory mechanism of the poly-L-Arg effect is likely to be dependent on energy-requiring cellular processes.
-
Analysis of transient and reversible effects of poly-L-arginine on the in vivo nasal absorption of FITC-dextran in rats. Reviewed
Ohtake K, Natsume H, Ueda H, Morimoto Y.
J Control Release 21 263 - 275 2002.04
Authorship：Lead author Language：English Publishing type：Research paper (scientific journal)
-
市販ビートルート粉末に含まれる硝酸塩量と抗酸化能の比較
薗田邦博 河野有華 大竹一男 清水彩子 柴 祥子 飯野汐里 加園恵三 小林 順
金城学院大学論集(自然科学編) 21 ( (1) ) 1 - 6 2024.09
Language：Japanese Publishing type：Research paper (bulletin of university, research institution)
-
英国と日本国内のビートルートジュースに含まれる硝酸塩と抗酸化能(ORAC値)の比較
河野 有華, 薗田 邦博, 清水 彩子, 大竹 一男, 飯野 汐里, 柴 祥子, 小林 順
金城学院大学論集(自然科学編) 20 ( 1 ) 26 - 33 2023.09
Language：Japanese Publisher：金城学院大学
英国で販売されているビートルートジュースと国内で購入できるビートルートジュースの硝酸塩、亜硝酸塩、抗酸化能(ORAC値)等を比較した。比較したのは製品A:英国販売ビートルートジュース(70mL)、製品B:国内販売ビートルートジュース(200mL)、製品C:国内販売ビートルートジュース(100mL)であった。亜硝酸イオン含有量は製品Aと製品Cは同程度であったが、製品Bと比較して有意に多かった。硝酸イオン含有量は製品A(328.3±19.9mg)、製品B(54.6±3.2mg)、製品C(87.5±2.1mg)で、製品Aに最も多く含まれていた。抗酸化能であるORAC値は100mLあたりの値では製品Bと製品Cと比べて製品Aが有意に値が高かったが、1製品当たりに換算すると製品Cと同程度となり、製品BのORAC値が高かった。ビートルートジュース製品であっても英国販売と国内販売のもので成分含有量が大幅に異なること、国内販売のものにも含有量に違いがあることが示された。
-
硝酸塩由来一酸化窒素補給を期待した市販野菜果物ジュース中の硝酸塩含有量と抗酸化能の比較
河野 有華, 薗田 邦博, 大竹 一男, 清水 彩子, 齋藤 百花, 柴 祥子, 加園 恵三, 小林 順
金城学院大学論集(自然科学編) 19 ( 1 ) 1 - 8 2022.09
Language：Japanese Publisher：金城学院大学
-
河野 有華, 薗田 邦博, 北森 一哉, 大竹 一男, 小林 順
日本内分泌学会雑誌 97 ( 5 ) 1503 - 1503 2022.03
Language：Japanese Publisher：(一社)日本内分泌学会
-
福祉・医療の現場から 高齢者に不足しがちな微量栄養素の補充による認知機能低下予防効果の検討(第2報) Reviewed
加園 恵三, 糸井 郁美, 本松 茂, 柴 祥子, 大竹 一男, 加藤 勇太
地域ケアリング 24 ( 1 ) 42 - 47 2022.01
Language：Japanese Publisher：(株)北隆館
日本は、2007年に65歳以上の高齢者人口が全体の21%を超え、超高齢社会に突入した。高齢者の増加に伴い、認知症患者数も増加の一途をたどっている。増加する認知症への対策として、認知症の前駆段階である軽度認知障害、あるいはそれ以前の段階で感知し、かつ、認知障害が進行しないための支援方法の確立は重要課題である。今回私どもは認知症の早期発見に、ADAS-Jcogが有用であること、また、高齢者に不足しがちな微量栄養素の補充による認知機能低下予防効果が期待できることを報告する。(著者抄録)
-
福祉・医療の現場から 高齢者に不足しがちな微量栄養素の補充による認知機能低下予防効果の検討(第2報) Reviewed
加園 恵三, 糸井 郁美, 本松 茂, 柴 祥子, 大竹 一男, 加藤 勇太
地域ケアリング 23 ( 6 ) 56 - 61 2021.06
Language：Japanese Publisher：(株)北隆館
日本は、2007年に65歳以上の高齢者人口が全体の21%を超え、超高齢社会に突入した。高齢者の増加に伴い、認知症患者数も増加の一途をたどっている。増加する認知症への対策として、認知症の前駆段階である軽度認知障害、あるいはそれ以前の段階で感知し、かつ、認知障害が進行しないための支援方法の確立は重要課題である。今回私どもは認知症の早期発見に、ADAS-Jcogが有用であること、また、高齢者に不足しがちな微量栄養素の補充による認知機能低下予防効果が期待できることを報告する。(著者抄録)
-
NO不足妊娠高血圧ラットの胎仔発育不全に対する亜硝酸塩補給の影響
薗田 邦博, 大竹 一男, 河野 有華, 小林 順
金城学院大学論集(自然科学編) 17 ( 2 ) 3 - 9 2021.03
Language：Japanese Publisher：金城学院大学
一酸化窒素(NO)合成阻害剤であるN-omega-nitro-L-arginine methyl ester(L-NAME)を用いたNO不足妊娠高血圧モデル動物を作成し、胎児発育不全(FGR)と胎盤構造に対する食事性亜硝酸塩の補給による影響を調査した。動物を、体重で4匹ずつControl(蒸留水)群、L-NAME(1g/L)群、L-NAME(1g/L)と亜硝酸ナトリウム(100mg/L)を混合した亜硝酸塩群の3群に無作為に分けた。L-NAMEや亜硝酸塩摂取による母体の体重、摂食量、摂水量、尿量について測定したが実験開始前と開始後で、各グループ間に有意な差はなかった。また、解剖時に母体重量、胎仔数、胎盤重量を測定した。その結果、各グループで有意な差は認められなかった。血圧においては、Control群に比べL-NAME群と亜硝酸塩群で有意に上昇したが、亜硝酸塩群はL-NAME群に比べ血圧の上昇を抑制した。各群における胎仔重量を比較したところ、Control群に比べL-NAME群で胎児体重の有意な減少が認められた。一方で、亜硝酸塩を補給したグループではControl群と有意な差は認められなかった。組織標本による胎盤の組織構造の変化を確認したところ、L-NAME群において母体と胎仔の栄養交換の場であるラビリンスゾーンの構造に空洞が多く確認された。一方で、亜硝酸塩群では構造の壊れている部分(空洞)が認められたもののL-NAME群に比べ少なかった。酸化ストレスマーカーである8-OHdGの尿中濃度は、Control群やL-NAME群に比べ亜硝酸塩群で有意に増加した。
-
福祉の現場から 高齢者に不足しがちな微量栄養素の補充による認知機能低下予防効果の検討(第2報) Reviewed
加園 恵三, 糸井 郁美, 本松 茂, 柴 祥子, 大竹 一男, 加藤 勇太
地域ケアリング 23 ( 2 ) 60 - 65 2021.02
Language：Japanese Publisher：(株)北隆館
日本は、2007年に65歳以上の高齢者人口が全体の21%を超え、超高齢社会に突入した。高齢者の増加に伴い、認知症患者数も増加の一途をたどっている。増加する認知症への対策として、認知症の前駆段階である軽度認知障害、あるいはそれ以前の段階で感知し、かつ、認知障害が進行しないための支援方法の確立は重要課題である。今回私どもは認知症の早期発見に、ADAS-Jcogが有用であること、また、高齢者に不足しがちな微量栄養素の補充による認知機能低下予防効果が期待できることを報告する。(著者抄録)
-
低酸素環境下トレーニングでの魚油濃縮物摂取によるヘモレオロジー的検討 Reviewed
櫛部 静二, 小林 悟, 新井 尚之, 浜崎 景, 野部 浩司, 竹之内 康広, 柴 祥子, 大竹 一男, 白幡 晶, 加園 恵三
脂質栄養学 29 ( 2 ) 127 - 135 2020.09
Language：Japanese Publisher：日本脂質栄養学会
-
高齢者に不足しがちな微量栄養素の補充による認知機能低下予防効果の検討 亜鉛と認知症の関連 Reviewed
加園 恵三, 柴 祥子, 大竹 一男, 加藤 勇太
細胞 52 ( 3 ) 130 - 134 2020.03
Language：Japanese Publisher：(株)ニュー・サイエンス社
現在、高齢化社会を迎えた日本では、認知症患者数は増加の一途をたどっている。増加する認知症への対策として、認知症の前駆段階である軽度認知障害、あるいはそれ以前の段階で感知し、かつ、認知障害が進行しないための支援方法の確立は重要課題である。筆者らは、これまでに高齢者では複数の栄養素が不足する可能性が高いことを報告した。今回筆者らは認知症の早期発見に、認知機能検査のADAS-Jcogが有用であること、また、高齢者に不足しがちな微量栄養素の補充による認知機能低下予防効果が期待できることを報告するとともに、亜鉛欠乏と認知機能障害との関連についても考察する。(著者抄録)
-
高齢者に不足しがちな微量栄養素の補充による認知機能低下予防効果の検討 Reviewed
加園恵三 糸井郁美 本松茂 高村亜矢乃 柴祥子 大竹一男 加藤勇太
別冊地域ケアリング 22 ( 1 ) 67 - 71 2020.01
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：北隆館
-
福祉の現場から 高齢者に不足しがちな微量栄養素の補充による認知機能低下予防効果の検討 Reviewed
加園 恵三, 糸井 郁美, 本松 茂, 高村 亜矢乃, 柴 祥子, 大竹 一男, 加藤 勇太
地域ケアリング 22 ( 1 ) 67 - 71 2020.01
Language：Japanese Publisher：(株)北隆館
現在、高齢化社会を迎えた日本では、認知症患者数は増加の一途をたどっている。増加する認知症への対策として、認知症の前駆段階である軽度認知障害、あるいはそれ以前の段階で感知し、かつ、認知障害が進行しないための支援方法の確立は重要課題である。今回私どもは認知症の早期発見に、ADAS-Jcogが有用であること、また、高齢者に不足しがちな微量栄養素の補充による認知機能低下予防効果が期待できることを報告する。(著者抄録)
-
絶食による廃用性腸管粘膜萎縮に及ぼす経口グルタチオン(GSH)投与の効果
内田 博之, 中島 由加里, 大竹 一男, 伊東 順太, 森田 匡彦, 神村 彩子, 小林 順
アミノ酸研究 12 ( 1 ) 59 - 60 2019.02
Language：Japanese Publisher：日本アミノ酸学会
-
Enhancement Effect of Poly-L-ornithine on the Nasal Absorption of Water-Soluble Macromolecules in Rats. Reviewed
Shigehiro Omori, Yusuke Kamiya, Tsutomu Yamaki, Masaki Uchida, Kazuo Ohtake, Mitsutoshi Kimura, Hideshi Natsume
Biological & pharmaceutical bulletin 42 ( 1 ) 144 - 148 2019
Language：English Publishing type：Research paper (scientific journal)
The transnasal route for the delivery of water-soluble macromolecules, such as bioactive peptides and proteins, has attracted interest, although the use of permeation enhancers is required due to the poor permeabilities of these macromolecules across the nasal mucosa. With polycationic compounds, such as poly-L-arginine and chitosan, the nasal absorption of hydrophilic macromolecules is molecular weight- and concentration-dependently enhanced without causing cytotoxicity. In the present study, we evaluated the effect of various molecular weights and concentrations of poly-L-ornithine (PLO), a polycationic compound, on the nasal absorption and the damage to the nasal mucosa in vivo. PLO enhanced the nasal absorption of fluorescein isothiocyanate-dextran (FD-4), used as a model drug, and the bioavailability of FD-4 increased with the concentration of PLO. The enhancement effect was also dependent on the molecular weight. The administration of PLO at a concentration that sufficed for enhancing the nasal absorption had no effect on the activity of lactic dehydrogenase and the protein leakage in the nasal fluid, as indices of nasal mucosa damage. These findings suggest that a transnasal delivery system using PLO is a useful strategy for improving the nasal absorption of water-soluble macromolecules without toxicity to the nasal mucosa.