研究者詳細 - 豊國　伸哉

論文 - 豊國　伸哉

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A processed grain food AOB inhibits hepatic injury in endotoxemic rats

Minamiyama, Y; Takemura, S; Toyokuni, S; Tanimoto, Y; Sato, EF; Inoue, M

BIOLOGICAL OXIDANTS AND ANTIOXIDANTS: MOLECULAR MECHANISMS AND HEALTH EFFECTS 頁： 349 - 357 1998年

A processed grain food inhibits hepatic injury in endotoxemic rats 査読有り

Minamiyama Y., Takemura S., Toyokuni S., Tanimoto Y., Sato E.F., Inoue M.

Journal of Nutritional Science and Vitaminology 44 巻 ( 4 ) 頁： 547 - 559 1998年

記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：Journal of Nutritional Science and Vitaminology

Although various antioxidants have been tested as therapeutics for endotoxemic subjects, the results of their efficacy are conflicting. Antioxidant biofactor (AOB) is a unique processed grain food that exhibits strong antioxidant activity (Minamiyama et al, J Nutr Sci Vitaminol, 40: 467- 477, 1994). The present study was carried out to test the effect of AOB on hepatic injury in rats induced by lipopolysaccharide (LPS). Intravenous administration of LPS induced liver injury with a concomitant increase in hepatic generation of nitric oxide (NO) and 4-hydroxy-2-nonenal (HNE) modified proteins in the control group. The administration of AOB significantly inhibited the LPS-induced hepatic injury and generation of HNE- modified proteins and increased the survival rate of endotoxemic rats without affecting NO generation and plasma levels of tumor necrosis factor-α (TNF- α) and interferon-γ (IFN-γ). AOB scavenged superoxide radicals without affecting NO production by LPS-stimulated macrophage cell line J 774.2 cells. AOB also inhibited lipid peroxidation induced by LPS in the cells. These results suggested that AOB might scavenge superoxide radicals and decrease toxic metabolites including HNE, thereby inhibiting liver injury in endotoxemic rats.

DOI： 10.3177/jnsv.44.547

その他リンク： https://jlc.jst.go.jp/DN/JALC/00085275768?from=CiNii

Oxidative stress and cancer: The role of redox regulation

Toyokuni S

BIOTHERAPY 11 巻 ( 2-3 ) 頁： 147 - 154 1998年

卵巣粘液性腫ようの術中腫よう捺印細胞像の検討境界悪性例を中心に:境界悪性例を中心に国際誌

清水恵子, 小椋聖子, 村田匡好, 高尾由美, 豊國伸哉, 桜井幹己

日本臨床細胞学会雑誌 37 巻 ( 6 ) 頁： 583 - 590 1998年

記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：特定非営利活動法人日本臨床細胞学会

卵巣腫瘍は良悪性の術前診断が困難なことが多く, 当院では術中腫瘍捺印細胞診を積極的に施行している. 1990年から1997年の8年間に術中腫瘍捺印細胞診が施行された卵巣粘液性腫瘍は34例で, 良性が16例, 境界悪性が12例, 悪性が6例であった. 術中腫瘍捺印細胞診の正診率は, 良性と悪性に関しては100%であったが, 境界悪性では75%で誤判定例はすべて良性と判定していた. 今回, われわれは境界悪性例を中心とした細胞像と, 誤判定を防ぐための新しい圧挫標本の併用について検討したので報告する.<BR>境界悪性腫瘍の細胞像の特徴は, 背景が比較的きれいで, 良性例に比べて重積性が増し, 乳頭状の集団やボール状の集団が出現していることであった. 個々の細胞異型に関しては, 良性例に比べてN/C比の増大や, 核クロマチン増量, 核小体の肥大が部分的に観察されるものの著明ではなく, 悪性例とは区別が可能と思われた. 良性と誤判定した例については, 上皮性成分の出現i数の少なさがその最大の原因と思われ, 圧挫標本の作製を加えることにより正診率の向上が期待できるものと思われた.

DOI： 10.5795/jjscc.37.583

CiNii Research

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Oxidative stress and cancer: The role of redox regulation 査読有り

S Toyokuni

BIOTHERAPY 11 巻 ( 2-3 ) 頁： 147 - 154 1998年

Immunohistochemical detection of 4-hydroxy-2-nonenal-modified-protein adducts in human alcoholic liver diseases

Ohhira M., Ohtake T., Matsumoto A., Saito H., Ikuta K., Fujimoto Y., Ono M., Toyokuni S., Kohgo Y.

Alcoholism: Clinical and Experimental Research 22 巻 ( 3 SUPPL. 1 ) 1998年

記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：Alcoholism: Clinical and Experimental Research

4-Hydroxy-2-nonenal (HNE) is one of the major components of lipid peroxidation product and has been shown to react with proteins to form HNE-protein adducts. HNE-protein adducts are relatively stable and can be used as a marker of radical-mediated cellular damage. We report herein the immunohistochemical analysis of HNE-protein adducts in human alcoholic liver diseases using a specific monoclonal antibody HNEJ-2. Cytoplasm of hepatocytes and bile duct epithelia was positively stained for HNE-protein adducts, and the nucleus was negligibly stained. The immunohistochemical intensity of hepatocytes was classified into three groups: strong, moderate, and faint staining. Strong staining was found in 43% of alcoholic liver diseases and in 4% of viral liver diseases. Hepatocytes of alcoholic liver diseases contained a higher amount of HNE-protein adducts than those of viral liver diseases, and the difference was statistically significant (p = 0.005; χ2 test). Semiquantitative analysis of the histological intensities of HNE-protein adducts and iron indicated a significant positive correlation (p = 0.084; Spearman's rank correlation). The localization of HNE-protein adducts and iron in hepatocytes appeared to be identical. These data suggested the correlation between HNE-protein adducts and iron. Our results indicate that HNE-protein adducts, a marker of oxidative stress-induced damage, are increased in human alcoholic liver damage, and that hepatic siderosis may act on the production of free radicals. Copyright © 1998 by The Research Society on Alcoholism.

DOI： 10.1111/acer.1998.22.s3_part1.145s

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A processed grain food AOB inhibits hepatic injury in endotoxemic rats 査読有り国際誌

Minamiyama, Y, Takemura, S, Toyokuni, S, Tanimoto, Y, Sato, EF, Inoue, M

BIOLOGICAL OXIDANTS AND ANTIOXIDANTS: MOLECULAR MECHANISMS AND HEALTH EFFECTS 頁： 349 - 357 1998年

New biomarker evidence of oxidative DNA damage in patients with non-insulin-dependent diabetes mellitus

Leinonen J., Lehtimäki T., Toyokuni S., Okada K., Tanaka T., Hiai H., Ochi H., Laippala P., Rantalaiho V., Wirta O., Pasternack A., Alho H.

FEBS Letters 417 巻 ( 1 ) 頁： 150 - 152 1997年11月

記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：FEBS Letters

Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) has been reported to serve as a sensitive biomarker of oxidative DNA damage and also of oxidative stress. We have investigated oxidative DNA damage in patients with non-insulin-dependent diabetes mellitus (NIDDM) by urinary 8-OHdG assessments. We determined the total urinary excretion of and OHdG from 24 h urine samples of 81 NIDDM patients 9 years after the initial diagnosis and of 100 non-diabetic control subjects matched for age and gender. The total 24 h urinary excretion of 8-OHdG was markedly higher in NIDDM patients than in control subjects (68.2 ± 39.4 μg vs, 49.6 ± 37.7 μg, P= 0.001). High glycosylated hemoglobin was associated with a high level of urinary 8-OHdG. The increased excretion of urinary and OHdG is seen as indicating an increased systemic level of oxidative DNA damage in NIDDM patients.

DOI： 10.1016/S0014-5793(97)01273-8

Scopus

New biomarker evidence of oxidative DNA damage in patients with non-insulin-dependent diabetes mellitus

Leinonen J, Lehtimaki T, Toyokuni S, Okada K, Tanaka T, Hiai H, Ochi H, Laippala P, Rantalaiho V, Wirta O, Pasternack A, Alho H

FEBS LETTERS 417 巻 ( 1 ) 頁： 150 - 152 1997年11月

Protein modification by lipid peroxidation products: Formation of malondialdehyde-derived N epsilon-(2-propenal)lysine in proteins 査読有り国際誌

Uchida K, Sakai K, Itakura K, Osawa T, Toyokuni S

ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS 346 巻 ( 1 ) 頁： 45 - 52 1997年10月

Protein modification by lipid peroxidation products: Formation of malondialdehyde-derived N(ε)(2-propenal)lysine in proteins

Uchida K., Sakai K., Itakura K., Osawa T., Toyokuni S.

Archives of Biochemistry and Biophysics 346 巻 ( 1 ) 頁： 45 - 52 1997年10月

記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：Archives of Biochemistry and Biophysics

Malondialdehyde (MDA), a naturally occurring dialdehyde produced in the membrane lipid peroxidation, is known to react with lysine residues of proteins, but the MDA-lysine adducts generated in the proteins have not been characterized adequately. In the present study, we provide evidence that the enaminal-type MDA-lysine adduct, N(ε)-(2-propenal)lysine, is formed in human low-density lipoprotein (LDL) upon reaction with MDA or Cu2+. We found that the incubation of N(α)acetyllysine with MDA generated N(α)-acetyl-N(ε)- (2-propenal)lysine as the predominant product. In addition, a polyclonal antiserum raised against the MDA-modified protein was found to contain antibody populations that could be purified by affinity gel prepared by covalent attachment of N(α)-acetyl-N(ε)-(2-propenal)lysine. It was concluded that the affinity-purified anti-N(ε)-(2-propenal) lysine antibody was highly specific to the enaminal derivative of both lysine residues and phosphatidylethanolamine, based on the observations that (i) MDA was the only aldehyde which generated immunoreactive materials in proteins; (ii) among structurally defined MDA-lysine adducts tested, the antibody recognized the enaminal adduct only; and (iii) immunoreactivity to N(2-propenal)serine was still significant but much weaker than its reactivity to N-(2- propenal)ethanol- amine. Furthermore, analysis of antibody recognition sites with a variety of N-(2-propenal)alkylamines revealed that the mono-specific antibody recognized the N-2-propenal-N-ethyl moiety [-(CH2)2-NH-CH=CH - CHO] of enaminal adducts. Determination by a competitive enzyme-linked immunosorbent assay demonstrated that N(ε)-(2-propenal)lysine accounted for 33.7 and 3.1% of the lysine residues that disappeared during in vitro incubation of LDL with MDA and Cu2+, respectively. These results suggest that N(ε)-(2-propenal)lysine represents a major form of MDA covalently attached to proteins.

DOI： 10.1006/abbi.1997.0266

Scopus

Protein modification by lipid peroxidation products: Formation of malondialdehyde-derived N epsilon-(2-propenal)lysine in proteins 査読有り国際誌

Uchida K, Sakai K, Itakura K, Osawa T, Toyokuni S

ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS 346 巻 ( 1 ) 頁： 45 - 52 1997年10月

Enhanced hepatic lipid peroxidation in chronic hepatitis C. 国際誌

Kageyama, F; Kobayashi, Y; Kawasaki, T; Nakamura, H; Toyokuni, S; Uchida, K

HEPATOLOGY 26 巻 ( 4 ) 頁： 79 - 79 1997年10月

Impact of the protection from free radical injury in heat shock preconditioning against ischemia-reperfusion injury in steatotic rat livers.

Yamagami, K; Yamamoto, Y; Kume, M; Kimoto, S; Ozaki, N; Toyokuni, S; Yamaoka, Y

HEPATOLOGY 26 巻 ( 4 ) 頁： 844 - 844 1997年10月

Impact of the protection from free radical injury in heat shock preconditioning against ischemia-reperfusion injury in steatotic rat livers. 国際誌

Yamagami, K, Yamamoto, Y, Kume, M, Kimoto, S, Ozaki, N, Toyokuni, S, Yamaoka, Y

HEPATOLOGY 26 巻 ( 4 ) 頁： 844 - 844 1997年10月

Enhanced hepatic lipid peroxidation in chronic hepatitis C. 査読有り国際誌

Kageyama F, Kobayashi Y, Kawasaki T, Nakamura H, Toyokuni S, Uchida K

HEPATOLOGY 26 巻 ( 4 ) 頁： 79 - 79 1997年10月

Induction and nuclear translocation of thioredoxin by oxidative damage in the mouse kidney: Independence of tubular necrosis and sulfhydryl depletion

Tanaka T., Nishiyama Y., Okada K., Hirota K., Matsui M., Yodoi J., Hiai H., Toyokuni S.

Laboratory Investigation 77 巻 ( 2 ) 頁： 145 - 155 1997年8月

記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：Laboratory Investigation

Adult T-cell leukemia-derived factor (ADF), originally defined as an interleukin-2 receptor inducer, is a human thioredoxin (TRX). ADF/TRX is a conserved multifunctional reductant presumably associated with redox regulation of the cellular environment; it works in vitro as a cytokine, free radical scavenger, activator of transcription factors, and substrate for several enzymes. In the present series of experiments, we studied the expression and intracellular localization of ADF/TRX in mouse kidney from two different renal tubular injury models: a free radical-associated model with ferric nitrilotriacetate (Fe-NTA) and a free radical-independent model with HgCI2. Markers of oxidative damage, such as 8-hydroxy-2'-deoxyguanosine, thiobarbituric acid-reactive substances, and 4-hydroxy-2-nonenal-modified proteins, were significantly increased in kidney from male C57BL/6 mice 1 hour after a single intraperitoneal injection of Fe-NTA (5 mg iron/kg). However, in kidney from mice given a subcutaneous injection of HgCI2 (5 mg Hg/kg), none of these markers were increased, despite tubular necrosis with sulfhydryl depletion. In the Fe-NTA model only, Northern and Western blot analyses of the kidney revealed induction of ADF/TRX (> 2.5-fold) after 16 hours and translocation of ADF/TRX from the cytoplasmic to nuclear fraction (> 3.5-fold) after 24 hours. Immunohistochemistry showed a catchy distribution of ADF/TRX in the normal renal proximal tubules. In ex vivo experiments using serial normal kidney frozen sections, it was found mat renal proximal tubules with low expression of ADF/FRX were more vulnerable to oxidative stress mediated by Fe-NTA. Collectively, these data suggest that: (a) ADF/TRX is induced and translocated to nuclei by oxidative damage mediated by Fe-NTA in the renal proximal tubules: (b) induction of ADF/TRX is independent of tubular necrosis or sulfhydryl depletion; and (c) ADF/TRX is involved in the cellular defense mechanisms in vive against oxidative damage.

Scopus

Induction and nuclear translocation of thioredoxin by oxidative damage in the mouse kidney: Independence of tubular necrosis and sulfhydryl depletion

Tanaka T, Nishiyama Y, Okada K, Hirota K, Matsui M, Yodoi J, Hiai H, Toyokuni S

LABORATORY INVESTIGATION 77 巻 ( 2 ) 頁： 145 - 155 1997年8月

Induction and nuclear translocation of thioredoxin by oxidative damage in the mouse kidney: independence of tubular necrosis and sulfhydryl depletion.

Tanaka T, Nishiyama Y, Okada K, Hirota K, Matsui M, Yodoi J, Hiai H, Toyokuni S

Laboratory investigation; a journal of technical methods and pathology 77 巻 ( 2 ) 頁： 145 - 55 1997年8月

Biomarker evidence of DNA oxidation in lung cancer patients: Association of urinary 8-hydroxy-2'-deoxyguanosine excretion with radiotherapy, chemotherapy, and response to treatment

Erhola M., Toyokuni S., Okada K., Tanaka T., Hiai H., Ochi H., Uchida K., Osawa T., Nieminen M.M., Alho H., Kellokumpu-Lehtinen P.

FEBS Letters 409 巻 ( 2 ) 頁： 287 - 291 1997年6月

記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：FEBS Letters

Ratios of urinary 8-hydroxy-2'-deoxyguanosine to urinary creatinine (8-OHdG/creatinine) have been considered as a good biological indicator of DNA oxidation. Urinary 8-OHdG/creatinine levels of lung cancer patients were evaluated by enzyme-linked immunosorbent assay using a monoclonal antibody N45.1 during radiotherapy and chemotherapy. An increase in urinary 8-OHdG/creatinine was found in non-small-cell carcinoma (non-SCC) patients during the course of radiotherapy. SCC patients showed higher levels of urinary 8-OHdG/creatinine than the controls. Furthermore, SCC patients with complete or partial response to the chemotherapy showed a significant decrease in urinary 8-OHdG/creatinine while patients with no change or progressive disease showed an increase.

DOI： 10.1016/S0014-5793(97)00523-1

Scopus

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