Faculty Profiles - TOYOKUNI Shinya

Papers - TOYOKUNI Shinya

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Oxydative stress persists in nearby LV area after myocardial infarction (MI) and shows two peaks

Miwa S, Toyokuni S, Tanaka S, Nishina T, Nomoto T, Yamazaki K, Ueda K, Nishimura K

CIRCULATION Vol. 106 ( 19 ) page： 312 - 312 2002.11

A novel method of "preparative" myocardial protection using green tea polyphenol in oral uptake

Miwa S, Saito M, Yamazaki K, Toyokuni S, Hyon SH, Fujita M, Komeda M

CIRCULATION Vol. 106 ( 19 ) page： 345 - 345 2002.11

Ex vivo whole-embryo culture of caspase-8-dificient embryos normalize their aberrant phenotypes in the developing neural tube and heart Reviewed

Sakamaki K, Inoue T, Asano M, Sudo K, Kazama H, Sakagami J, Sakata S, Ozaki M, Nakamura S, Toyokuni S, Osumi N, Yonehara S

Cell Death and Differentiation Vol. 9 ( 11 ) page： 1196 - 1206 2002.11

Comparison between high-performance liquid chromatography and enzyme-linked Immunosorbent assay for the determination of 8-hydroxy-2 '-deoxyguanosine in human urine

Shimoi K, Kasai H, Yokota N, Toyokuni S, Kinae N

CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Vol. 11 ( 8 ) page： 767 - 770 2002.8

Spaciotemporal alteration of 8-hydroxy-2'-deoxyguanosine levels in cardiomyocytes after myocardial infarction in rats. Reviewed International journal

Senri Miwa, Shinya Toyokuni, Takeshi Nishina, Takuya Nomoto, Makoto Hiroyasu, Kazunobu Nishimura, Masashi Komeda

Free radical research Vol. 36 ( 8 ) page： 853 - 858 2002.8

Language：English Publishing type：Research paper (scientific journal) Publisher：TAYLOR & FRANCIS LTD

Temporary or persistent heart failure is one of the major complications after myocardial infarction (MI). In order to elucidate the pathogenesis of MI, we studied the spaciotemporal alteration of 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in cardiomyocytes in a rat model of ligation of the left anterior descending branch of the coronary artery The lethality in this model was 18%. Hearts were dissected at 0, 3, 6, 12, 24, 48 h, and 1, 2, 4, 6 weeks after the operation. The cardiac level of 8-OHdG was evaluated biochemically as well as by immunohistochemistry with monoclonal antibody N45.1. Three to 6h after ligation, the 8-OHdG levels were increased in the cardiomyocytes of MI (six-fold) and peri-MI (four-fold) areas. After 24h, the myocardium in the MI area was necrotized, and thereafter the 8-OHdG level decreased. 8-OHdG levels in the myocardium of peri-MI areas returned once to a normal level, but were significantly increased at 2-4 weeks along with the appearance of apoptotic cardiomyocytes in this area. The heart after MI has been generally considered as clinically stable after four weeks. However, cardiomyocytes near the infarcted area were oxidatively stressed even after four weeks when the affected lesion was extensive. The present data support the use of supplementary antioxidant therapies to save functional myocardium after MI. (213 words).

DOI： 10.1081/1071576021000005285

Vitamin D receptor activity and prevention of colonic hyperproliferation and oxidative stress

Kallay E, Bareis P, Bajna E, Kriwanek S, Bonner E, Toyokuni S, Cross HS

FOOD AND CHEMICAL TOXICOLOGY Vol. 40 ( 8 ) page： 1191 - 1196 2002.8

Protective effect of colored rice over white rice on fenton reaction-based renal lipid peroxidation in rats (vol 36, pg 583, 2002)

Toyokuni, S; Itani, T; Morimitsu, Y; Okada, K; Ozeki, M; Kondo, S; Uchida, K; Osawa, T; Hiai, H; Tashiro, T

FREE RADICAL RESEARCH Vol. 36 ( 8 ) 2002.8

Comparison between high-performance liquid chromatography and enzyme-linked immunosorbent assay for the determination of 8-hydroxy-2'-deoxyguanosine in human urine. International journal

Kayoko Shimoi, Hiroshi Kasai, Naoko Yokota, Shinya Toyokuni, Naohide Kinae

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology Vol. 11 ( 8 ) page： 767 - 70 2002.8

Language：English Publishing type：Research paper (scientific journal)

8-Hydroxy-2'-deoxyguanosine (8-OH-dG), which has been regarded as a potential marker of oxidative DNA damage induced by reactive oxygen species, was measured in human urine by a commercial ELISA using a monoclonal antibody N45.1 and by high-performance liquid chromatography (HPLC) coupled to an electrochemical detector (HPLC-ECD) to evaluate whether the ELISA system is applicable to human monitoring studies. The urine samples were collected from 120 healthy men ages 18-58 in a steel-manufacturing company. A good correlation (r = 0.833; P < 0.0001) was observed between the two methods on HPLC-purified 8-OH-dG fractions from 23 urine samples. The mean value (+/-SD) of 8-OH-dG (microg/g creatinine) was 5.47 (+/-2.97) by HPLC-ECD assay and 5.50 (+/-2.36) by ELISA. However, the correlation (r) between the two methods on 120 original urine samples was 0.460 [P < 0.001; mean value (+/-SD) of 8-OH-dG (microg/g creatinine) was 4.46 (+/-2.03) by the HPLC assay and 9.33 (+/-3.23) by ELISA]. ELISA estimates were about 2-fold higher than the HPLC estimates on original urine. For an unknown reason, 10% of the urine samples showed more than a 4-fold increase in value by ELISA. It is suggested that the ELISA system is applicable for comparative human monitoring studies. Prepurification of 'samples is required to determine the absolute value of 8-OH-dG in individual urine samples by ELISA.

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Comparison between high-performance liquid chromatography and enzyme-linked immunosorbent assay for the determination of 8-hydroxy-2'-deoxyguanosine in human urine.

Shimoi K, Kasai H, Yokota N, Toyokuni S, Kinae N

Inhibition of gastric inhibitory polypeptide signaling prevents obesity. Reviewed International journal

Kazumasa Miyawaki, Yuichiro Yamada, Nobuhiro Ban, Yu Ihara, Katsushi Tsukiyama, Heying Zhou, Shimpei Fujimoto, Akira Oku, Kinsuke Tsuda, Shinya Toyokuni, Hiroshi Hiai, Wataru Mizunoya, Tohru Fushiki, Jens Juul Holst, Mitsuhiro Makino, Akira Tashita, Yukari Kobara, Yoshiharu Tsubamoto, Takayoshi Jinnouchi, Takahito Jomori, Yutaka Seino

Nature medicine Vol. 8 ( 7 ) page： 738 - 742 2002.7

Language：English Publishing type：Research paper (scientific journal)

Secretion of gastric inhibitory polypeptide (GIP), a duodenal hormone, is primarily induced by absorption of ingested fat. Here we describe a novel pathway of obesity promotion via GIP. Wild-type mice fed a high-fat diet exhibited both hypersecretion of GIP and extreme visceral and subcutaneous fat deposition with insulin resistance. In contrast, mice lacking the GIP receptor (Gipr(-/-)) fed a high-fat diet were clearly protected from both the obesity and the insulin resistance. Moreover, double-homozygous mice (Gipr(-/-), Lep(ob)/Lep(ob)) generated by crossbreeding Gipr(-/-) and obese ob/ob (Lep(ob)/Lep(ob)) mice gained less weight and had lower adiposity than Lep(ob)/Lep(ob) mice. The Gipr(-/-) mice had a lower respiratory quotient and used fat as the preferred energy substrate, and were thus resistant to obesity. Therefore, GIP directly links overnutrition to obesity and it is a potential target for anti-obesity drugs.

DOI： 10.1038/nm727

Vitamin D receptor activity and prevention of colonic hyperproliferation and oxidative stress

Kállay E., Bareis P., Bajna E., Kriwanek S., Bonner E., Toyokuni S., Cross H.

Food and Chemical Toxicology Vol. 40 ( 8 ) page： 1191 - 1196 2002.6

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Food and Chemical Toxicology

Unimpaired vitamin D action has been implicated in human cancer prevention. We have previously demonstrated the effectiveness of 1α-dihydroxyvitamin D3 (1,25-D3) to reduce proliferation and increase differentiation in human colon cancer cells. The aim of this study was to investigate, on the one hand, expression of the vitamin D receptor (VDR) and of 25-hydroxyvitamin D3-1α-hydroxylase (1α-hydroxylase) in human normal and malignant colonic tissue and, on the other hand, to determine consequences of reduced or lacking VDR action in a VDR knockout mouse model. In low-grade malignancies of the human colon we found increased VDR and 1α-hydroxylase mRNA expression. However, in late-stage high-grade tumors the vitamin D system is severely compromised. In the mouse colon we found an inverse relationship between VDR levels and proliferation in colon descendens, a tissue known to be specifically affected by nutrients during carcinogenesis. Expression of 8-hydroxy-2′-deoxyguanosine (8-OHdG), a marker of oxidative DNA damage, was significantly augmented with complete loss of VDR. These data suggest that genomic 1,25-D3 action is necessary to protect against nutrition-linked hyperproliferation and oxidative DNA damage. © 2002 Elsevier Science Ltd. All rights reserved.

DOI： 10.1016/S0278-6915(02)00030-3

Scopus

Carvedilol decreases elevated oxidative stress in human failing myocardium

Nakamura, K; Kusano, K; Nakamura, Y; Kakishita, M; Ohta, K; Nagase, S; Yamamoto, M; Miyaji, K; Saito, H; Morita, H; Emori, T; Matsubara, H; Toyokuni, S; Ohe, T

CIRCULATION Vol. 105 ( 24 ) page： 2867 - 2871 2002.6

Peroxynitrite-mediated stress is associated with proliferation of human metastatic colorectal carcinoma in the liver

Kondo S, Toyokuni S, Tsuruyama T, Ozeki M, Tachibana T, Echizenya M, Hiai H, Onodera H, Imamura M

CANCER LETTERS Vol. 179 ( 1 ) page： 87 - 93 2002.5

Peroxynitrite-mediated stress is associated with proliferation of human metastatic colorectal carcinoma in the liver.

Kondo S, Toyokuni S, Tsuruyama T, Ozeki M, Tachibana T, Echizenya M, Hiai H, Onodera H, Imamura M

Cancer letters Vol. 179 ( 1 ) page： 87 - 93 2002.5

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

3-Nitrotyrosine (3-NT), a product of peroxynitrite reaction, is abundantly observed in hepatocytes adjacent to human metastatic colorectal carcinoma. To elucidate its biological significance, we undertook to identify nitric oxide (NO)-producing cells and apoptosis under oxidative stress. We observed strong inducible NO-synthase (iNOS) immunoreactivity in the hepatocytes adjacent to metastatic tumor, revealing an identical pattern to 3-NT immunostaining. Furthermore, intense 3-NT immunostaining of hepatocytes was associated with apoptosis whereas carcinoma cells near those hepatocytes presented high proliferating-cell nuclear antigen. Our results suggest that contact of metastatic tumor induces apoptosis in adjacent hepatocytes through peroxynitrite, thus permitting the proliferation of cancer cells. © 2002 Elsevier Science Ireland Ltd. All rights reserved.

DOI： 10.1016/s0304-3835(01)00859-x

Scopus

PubMed

Peroxynitrite-mediated stress is associated with proliferation of human metastatic colorectal carcinoma in the liver. International journal

Shohei Kondo, Shinya Toyokuni, Tatsuaki Tsuruyama, Munetaka Ozeki, Tsuyoshi Tachibana, Michiko Echizenya, Hiroshi Hiai, Hisashi Onodera, Masayuki Imamura

Cancer letters Vol. 179 ( 1 ) page： 87 - 93 2002.5

Language：English Publishing type：Research paper (scientific journal)

PubMed

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Isolation and characterization of annexin 2 pseudogene in Rattus norvegicus

Ozeki M, Hoshino S, Hiai H, Toyokuni S

GENE Vol. 289 ( 1-2 ) page： 185 - 190 2002.5

Isolation and characterization of annexin 2 pseudogene in Rattus norvegicus.

Ozeki M, Hoshino S, Hiai H, Toyokuni S

Gene Vol. 289 ( 1-2 ) page： 185 - 90 2002.5

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

Annexin 2 is a calcium-regulated, phospholipid-binding protein present in endothelial cells, macrophages and some tumor cells. Annexin 2 is a substrate for a variety of protein kinases, and plays roles in the regulation of endocytosis, exocytosis and thrombolysis. We have determined the nucleotide sequence of a rat genomic DNA fragment that hybridized to a rat annexin 2 DNA complementary to RNA (cDNA) probe. Sequence analysis revealed that it was an intronless rat annexin 2, consisting of a start-to-stop-codon-length copy of the processed transcript. This pseudogene contained 33 point mutations and two deletion sites in the coding region as compared with the cDNA, and thus displayed typical features of a retroposon. Transitions were more frequent than transversions, and the most frequent type of mutation was G to A transition. We isolated a phage clone that contained a functional rat annexin 2 genomic fragment including coding exons 3 and 4. Polymerase chain reaction and subsequent sequence analysis revealed an intron of approximately 4 kbp at the same site as in humans and mice. Whereas the annexin 2 gene or its cDNA homologues have been detected in various species from Xenopus to humans, its pseudogene has been reported only in humans. In the present study, we demonstrated the presence of an annexin 2 pseudogene in rats. © 2002 Elsevier Science B.V. All rights reserved.

DOI： 10.1016/s0378-1119(02)00549-8

Scopus

PubMed

Isolation and characterization of annexin 2 pseudogene in Rattus norvegicus. International journal

Munetaka Ozeki, Shinsuke Hoshino, Hiroshi Hiai, Shinya Toyokuni

Gene Vol. 289 ( 1-2 ) page： 185 - 90 2002.5

Language：English Publishing type：Research paper (scientific journal)

PubMed

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Hepatocyte nuclear factor-1 alpha recruits the transcriptional co-activator p300 on the GLUT2 gene promoter

Ban N, Yamada Y, Someya Y, Miyawaki K, Ihara Y, Hosokawa M, Toyokuni S, Tsuda K, Seino Y

DIABETES Vol. 51 ( 5 ) page： 1409 - 1418 2002.5

Inhibitory effect of a novel water-soluble vitamin E derivative on atherosclerosis in rabbits

Yoshida N, Murase H, Kunieda T, Toyokuni S, Tanaka T, Terao J, Naito Y, Tanigawa T, Yoshikawa T

ATHEROSCLEROSIS Vol. 162 ( 1 ) page： 111 - 117 2002.5

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Papers - TOYOKUNI Shinya