Faculty Profiles - TOYOKUNI Shinya

Papers - TOYOKUNI Shinya

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Heat-shock preconditioning reduces oxidative protein denaturation andameliorates liver injury by carbon tetrachloride in rats Reviewed International journal

YAMAMOTO H.

Res. Exp. Med. Vol. 199 ( 6 ) page： 309 - 318 2000.6

Expression of stress-response and cell proliferation genes in renal cell carcinoma induced by oxidative stress

TANAKA T.

Am. J. Pathol. Vol. 156 ( 6 ) page： 2149 - 2157 2000.6

Effects of geranyl-geranyl-acetone administration before heat shock preconditioning for conferring tolerance against ischemia-reperfusion injury in rat livers

Yamagami K, Yamamoto Y, Ishikawa Y, Yonezawa K, Toyokuni S, Yamaoka Y

JOURNAL OF LABORATORY AND CLINICAL MEDICINE Vol. 135 ( 6 ) page： 465 - 475 2000.6

Detection of lipofuscin-like fluorophore in oxidized human low-density lipoprotein. 4-Hydroxy-2-nonenal as a potential source of fluorescent chromophore

Itakura K., Oya-Ito T., Osawa T., Yamada S., Toyokuni S., Shibata N., Kobayashi M., Uchida K.

FEBS Letters Vol. 473 ( 2 ) page： 249 - 253 2000.5

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：FEBS Letters

It has recently been shown that the lipid peroxidation product 4- hydroxy-2-nonenal (HNE) forms a fluorescent hydroxyiminodihydropyrrole derivative with the ε-amino group of lysine residue. In this study, we raised a monoclonal antibody (mAb2C12) directed to the fluorophore-protein conjugate and found that the antibody was specific to the chromophore structure of the compound. Immunohistochemical analysis of atherosclerotic lesions from the human aorta showed that the fluorophore was indeed present in the lesions, in which intense positivity was primarily associated with macrophage-derived foam cells and thickening of the neointima of the arterial walls. Antigenic materials were also detected in the oxidatively modified low-density lipoprotein (LDL) with Cu2+ and in the oxidatively modified bovine serum albumin with an iron/linoleic acid autoxidation system, indicating that the HNE, which originated from the peroxidation of polyunsaturated fatty acids, could be a potential source of the fluorescent chromophore in oxidized LDL. (C) 2000 Federation of European Biochemical Societies.

DOI： 10.1016/S0014-5793(00)01539-8

Scopus

Detection of lipofuscin-like fluorophore in oxidized human low-density lipoprotein - 4-Hydroxy-2-nonenal as a potential source of fluorescent chromophore

Itakura K, Oya-Ito T, Osawa T, Yamada S, Toyokuni S, Shibata N, Kobayashi M, Uchida K

FEBS LETTERS Vol. 473 ( 2 ) page： 249 - 253 2000.5

Antioxidant alpha-tocopherol ameliorates glycemic control of GK rats, a model of type 2 diabetes. Reviewed International journal

Ihara Y, Yamada Y, Toyokuni S, Miyawaki K, Ban N, Adachi T, Kuroe A, Iwakura T, Kubota A, Hiai H, Seino Y

FEBS letters Vol. 473 ( 1 ) page： 24 - 6 2000.5

Language：English Publishing type：Research paper (scientific journal) Publisher：FEBS Letters

We have shown recently that oxidative stress by chronic hyperglycemia damages the pancreatic β-cells of GK rats, a model of non-obese type 2 diabetes, which may worsen diabetic condition and suggested the administration of antioxidants as a supportive therapy. To determine if natural antioxidant α-tocopherol (vitamin E) has beneficial effects on the glycemic control of type 2 diabetes, GK rats were fed a diet containing 0, 20 or 500 mg/kg diet α-tocopherol. Intraperitoneal glucose tolerance test revealed a significant increment of insulin secretion at 30 min and a significant decrement of blood glucose levels at 30 and 120 min after glucose loading in the GK rats fed with high α-tocopherol diet. The levels of glycated hemoglobin A1c, an indicator of glycemic control, were also reduced. Vitamin E supplementation clearly ameliorated diabetic control of GK rats, suggesting the importance of not only dietary supplementation of natural antioxidants but also other antioxidative intervention as a supportive therapy of type 2 diabetic patients. Copyright (C) 2000 Federation of European Biochemical Societies.

DOI： 10.1016/s0014-5793(00)01489-7

Web of Science

Scopus

PubMed

Antioxidant α-tocopherol improves glycemic control of GK rats, a model of type 2 diabetes

Ihara, Y; Yamada, Y; Toyokuni, S; Ban, N; Kuroe, A; Seino, Y

DIABETES Vol. 49 page： A429 - A429 2000.5

Upregulation of thioredoxin (TRX) expression in giant cell myocarditis in rats. Reviewed International journal Open Access

Shioji K, Kishimoto C, Nakamura H, Toyokuni S, Nakayama Y, Yodoi J, Sasayama S

FEBS letters Vol. 472 ( 1 ) page： 109 - 13 2000.4

Language：English Publishing type：Research paper (scientific journal) Publisher：FEBS Letters

To examine the possible involvement of a redox regulating mechanism in the pathogenesis of immune-mediated myocarditis, myocarditis was induced by immunization of porcine cardiac myosin in rats and immunohistochemistry and Western blot for thioredoxin (TRX) were performed. Immunohistochemistry for 8-hydroxy-2'-deoxyguanosine (8-OHdG) and nuclear factor kappa-B (NF-κB) was also performed. TRX was upregulated in the acute stage, but not in the chronic stage, and the expression was correlated with the severity of the disease. Damaged myocytes were strongly immunostained for 8-OHdG and NF-κB. Thus, TRX may be specifically induced by acute inflammatory stimuli, and the development of acute immune-mediated myocarditis may be regulated by the cellular redox state via TRX. Copyright (C) 2000 Federation of European Biochemical Societies.

DOI： 10.1016/s0014-5793(00)01446-0

Web of Science

Scopus

PubMed

Upregulation of thioredoxin (TRX) expression in giant cell myocarditis in rats

SHIOJI K

FEBS Lett Vol. 472 ( 1 ) page： 109 - 113 2000.4

Successful interferon therapy reverses enhanced hepatic iron accumulation and lipid peroxidation in chronic hepatitis C International journal

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

AMERICAN JOURNAL OF GASTROENTEROLOGY Vol. 95 ( 4 ) page： 1041 - 1050 2000.4

Overexpression of the hOGG1 gene and high 8-hydroxy-2 '-deoxyguanosine (8-OHdG) lyase activity in human colorectal carcinoma: Regulation mechanism of the 8-OHdG level in DNA

Kondo S, Toyokuni S, Tanaka T, Hiai H, Onodera H, Kasai H, Imamura M

CLINICAL CANCER RESEARCH Vol. 6 ( 4 ) page： 1394 - 1400 2000.4

Successful interferon therapy reverses enhanced hepatic iron accumulation and lipid peroxidation in chronic hepatitis C Reviewed International journal Open Access

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

American Journal of Gastroenterology Vol. 95 ( 4 ) page： 1041 - 1050 2000.4

Language：English Publishing type：Research paper (scientific journal) Publisher：American Journal of Gastroenterology

OBJECTIVES: Hepatic iron deposition has been reported in chronic hepatitis C (CH-C), and iron-induced lipid peroxidation may be involved in the pathogenesis of CH-C. The aims of the present study were: 1) to determine whether patients with CH-C have evidence of enhanced hepatic lipid peroxidation and to evaluate its relation to iron status, compared with that in patients with chronic hepatitis B (CH-B); and 2) to assess the effect of interferon (IFN) therapy on hepatic iron and lipid peroxidation. METHODS: In the liver biopsies of 40 patients with CH-C and 26 patients with CH-B, immunohistochemical detection of 4-hydroxy-2-nonenal (HNE)-protein adducts for evaluation of lipid peroxidation was performed, and hepatic iron status was biochemically and histologically assessed. In 16 CH-C patients with normal serum transaminases and undetectable serum HCV-RNA >6 months after the end of IFN treatment (responders) and in 11 nonresponders, hepatic HNE- protein adducts and siderosis were evaluated in pre- and posttreatment liver biopsies. RESULTS: Hepatocytic HNE-protein adducts and iron deposits were more abundant in the patients with CH-C than in those with CH-B. No correlation was found between the levels of hepatocytic HNE-protein adducts and hepatic iron status in either of the two groups. In the responders to IFN treatment for CH-C, hepatocytic HNE-protein adducts disappeared or attenuated with improvement of hepatic siderosis after the treatment, whereas IFN treatment did not improve hepatocytic expression of HNE-protein adducts and hepatic siderosis in the nonresponders. CONCLUSIONS: Patients with CH-C have evidence of enhanced hepatic iron accumulation and lipid peroxidation compared to those with CH-B. In CH-C, hepatic siderosis and lipid peroxidation are improved with successful IFN treatment. These results suggest that hepatic lipid peroxidation and iron may potentially play contributory roles in the pathogenesis of CH-C. (C) 2000 by Am. Coll. of Gastroenterology.

DOI： 10.1016/S0002-9270(00)00771-1

Scopus

Successful interferon therapy reverses enhanced hepatic iron accumulation and lipid peroxidation in chronic hepatitis C International journal

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

AMERICAN JOURNAL OF GASTROENTEROLOGY Vol. 95 ( 4 ) page： 1041 - 1050 2000.4

Overexpression of the hOGG1 gene and high 8-hydroxy-2'-deoxyguanosine (8-OHdG) lyase activity in human colorectal carcinoma: Regulation mechanism of the 8-OHdG level in DNA Reviewed International journal

Kondo S., Toyokuni S., Tanaka T., Hiai H., Onodera H., Kasai H., Imamura M.

Clinical Cancer Research Vol. 6 ( 4 ) page： 1394 - 1400 2000.4

Language：English Publishing type：Research paper (scientific journal) Publisher：Clinical Cancer Research

8-Hydroxy-2'-deoxyguanosine (8-OHdG) is one of the most abundant oxidatively modified lesions in DNA. Our previous study (Kondo et al., Free Radic. Biol. Med., 27: 401-410, 1999) revealed that human colorectal carcinoma cells are oxidatively stressed based on 8-OHdG determination. To elucidate 8-OHdG metabolism and its clinical significance in colorectal carcinoma, we studied the 8-OHdG repair system in DNA by measuring specific lyase activity and hOGG1 expression using quantitative-competitive reverse transcription-PCR. In addition, we searched for the presence of mutations and single nucleotide polymorphisms of the hOGG1 gene by single-strand conformational polymorphism and sequencing analyses. It was found that 8- OHdG-specific lyase activity and hOGG1 expression were significantly up- regulated in carcinoma, and a proportional association between 8-OHdG levels and either 8-OHdG lyase activity (r = 0.641, P < 0.05) or hOGG1 expression (r = 0.702, P < 0.05) was present. Whereas no difference was detected in the 8- OHdG level between early- and advanced-stage cancer, lyase activity (1.2- fold) and hOGG1 expression (1.6-fold) were significantly increased in advanced-stage cancer. No mutation was found in the 25 tumors examined. Three kinds of single nucleotide polymorphism were observed, including that of codon 326 (Ser/Cys) in exon 7. However, there was no correlation between any of the three polymorphic patterns and either 8-OHdG level or lyase activity. These results suggest that increased 8-OHdG levels in colorectal carcinoma are attributed to increased formation and are maintained by induced 8-OHdG repair activity at appropriate high levels. Our results may offer a unique approach in the development of preventive and therapeutic interventions as well as new insights into the pathogenesis of colorectal carcinoma.

Scopus

Overexpression of the hOGG1 gene and high 8-hydroxy-2'-deoxyguanosine (8-OHdG) lyase activity in human colorectal carcinoma : regulation mechanism of the 8-OHdG level in DNA

KONDO S

Clin Cancer Res Vol. 6 ( 4 ) page： 1394 - 1400 2000.4

Overexpression of the hOGG1 gene and high 8-hydroxy-2'-deoxyguanosine (8-OHdG) lyase activity in human colorectal carcinoma: regulation mechanism of the 8-OHdG level in DNA.

Kondo S, Toyokuni S, Tanaka T, Hiai H, Onodera H, Kasai H, Imamura M

Clinical cancer research : an official journal of the American Association for Cancer Research Vol. 6 ( 4 ) page： 1394 - 400 2000.4

Cytoprotective effects of nitroglycerin in ischemia-reperfusion-induced lung injury

Kawashima M, Bando T, Nakamura T, Isowa N, Liu MY, Toyokuni S, Hitomi S, Wada H

AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE Vol. 161 ( 3 ) page： 935 - 943 2000.3

Formation of 8-hydroxy-2'-deoxyguanosine and 4-hydroxy-2-nonenal-modified proteins in rat liver after ischemia-reperfusion : distinct localization of the two oxidatively modified products

YAMAGAMI K

Antioxid Redox Signal Vol. 2 ( 1 ) page： 127 - 136 2000.1

Serum 4-Hydroxy-2-Nonenal-Modified Albumin Is Elevated in Patients with Type 2 Diabetes Mellitus Reviewed International journal

Toyokuni Shinya, Yamada Satoshi, Kashima Minoru, Ihara Yu, Yamada Yuichiro, Tanaka Tomoyuki, Hiai Hiroshi, Seino Yutaka, Uchida Koji

ANTIOXIDANTS & REDOX SIGNALING Vol. 2 ( 4 ) page： 681 - U65 2000

Formation of 8-Hydroxy-2 '-Deoxyguanosine and 4-Hydroxy-2-Nonenal-Modified Proteins in Rat Liver after Ischemia-Reperfusion: Distinct Localization of the Two Oxidatively Modified Products

Yamagami Kazuhiko, Yamamoto Yuzo, Kume Makoto, Ishikawa Yasuhide, Yamaoka Yoshio, Hiai Hiroshi, Toyokuni Shinya

ANTIOXIDANTS & REDOX SIGNALING Vol. 2 ( 1 ) page： 127 - 136 2000

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Papers - TOYOKUNI Shinya