63

D e p a r t m e n t o f I m m u n o b i o l o g y a n d N e u r o s c i e n c e

64

Division of Immunogenetics

65

66

1. Nishikimi A, Fukuhara H, Su W, Hongu T, Takasuga S, Mihara H, Cao Q, Sanematsu F, Kanai M,

Hasegawa H, Tanaka Y, Shibasaki M, Kanaho Y, Sasaki T, Frohman MA, Fukui Y. 2009

Sequential regulation of DOCK2 dynamics by two phospholipids during neutrophil chemotaxis.

Science in press

2. Nakasaki T, Tanaka T, Okudaira S, Hirosawa M, Umemoto E, Otani K, Jin S, Bai Z, Hayasaka H, Fukui

Y, Aozasa K, Fujita N, Tsuruo T, Ozono K, Aoki J, Miyasaka M. 2008.

Involvement of lysophosphatidic acid-generating enzyme autotaxin in lymphocyte-endothelial cell

interactions.

Am. J. Pathol., 173, 1566-1576.

3. Gotoh K, Tanaka Y, Nishikimi A, Inayoshi A, Enjoji M, Takayanagi R, Sasazuki T, Fukui Y. 2008.

Differential requirement for DOCK2 in migration of plasmacytoid dendritic cells versus myeloid

dendritic cells.

Blood. 111, 2973-2976.

4. Kikuchi T, Kubonishi S, Shibakura M, Namba N, Matsui T, Fukui Y, Tanimoto M, Katayama Y. 2008.

Dock2 participates in bone marrow lympho-hematopoiesis.

Biochem. Biophys. Res. Commun. 367, 90-96.

67

1. Fukui Y(2009 2/15-2/16)

Molecular mechanism controlling intracellular DOCK2 dynamics during neutrophil chemotazxis.

The 3rd

Global COE International Symposium Singapore

2. Fukui Y (2008 11/3-11/6).

Immune regulatory function of DOCK2 in health and disease.

Japan-German Immunology Seminar 2008,

68

11. Tanaka Y, Fukui Y (2008 11/9-11/10).

T helper type 2 differentiation and intracellular trafficking of the interleukin 4 receptor- subunit

controlled by the Rac activator DOCK2.

The 2nd Global COE International Symposium joint with the 18th Hot Spring Harbor Symposium of

Medical Institute of Bioregulation,

12. Gotoh K, Tanaka Y, Nishikimi A, Fukui Y(2008 9/7-9/11).

Differential requirement for DOCK2 in migration of plasmacytoid dendritic cells versus myeloid

dendritic cells.

8

69

Division of Clinical Immunology

70

71

Ikuyama S, Imamura-Takase E, Tokunaga S, Oribe M, Nishimura J. 2009.

Sixty percent of patients with rheumatoid arthritis in Japan have used dietary supplements or health

foods.

Modern Rheumatol, in press.

Yoshida A, Hisatome I, Taniguchi S, Shirayoshi Y, Yamamoto Y, Miake J, OhkuraT, Akama T,

Igawa O, Shigemasa C, Kamijo K, Ikuyama S, Caturegli P, Suzuki K. 2009.

Pendrin is a novel autoantigen recognized by patients with autoimmune thyroid diseases.

J Clin Endocrinol Metab 94,442-448.

Shiratsuchi M, Motomura S, Abe Y, Shiokawa S, Nishimura J. 2008.

Long-term follow-up after nonmyeloablative allogeneic hematopoietic stem cell transplantation for

systemic sclerosis.

Clin Rheumatol. 27, 1207-1209.

Tanigawa K, Suzuki K, Nakamura K, Akama T, Kawashima A, Wu H, Hayashi M,Takahashi S,

Ikuyama S, Ito T, Ishi N. 2008.

Expression of adipose differentiation-related protein (ADRP) and perilipin in macrophages infected

with Mycobacterium leprae.

FEMS Microbiol Lett.289,72-79.

Xiao Y, Motomura S, Podack ER. 2008.

APRIL (TNFSF13) regulates collagen-induced arthritis, IL-17 production and Th2 response.

Eur J Immunol. 38,3450-3458.

Gondo S, Okabe T, Tanaka T, Morinaga H, Nomura M, Takayanagi R, Nawata H, Yanase T.

2008.

Adipose tissue-derived and bone marrow-derived mesenchymal cells develop

into different lineage of steroidogenic cells by forced expression of steroidogenic factor 1.

Endocrinology 149,4717-4725.

Gu JQ, Ikuyama S, Wei P, Fan B, Oyama J, Inoguchi T, Nishimura J. 2008.

Pycnogenol, an extract from French maritime pine, suppresses Toll-like receptor 4-mediated expression

of adipose differentiation-related protein in macrophages.

Am J Physiol Endocrinol Metab, 295,E1390-E1400.

Shirohzu H, Okabe T, Gondo S, Tanaka T, Ohe K, Morinaga H, Kawate H, Nomura M,Takayanagi

R, Nawata H, Yanase T. 2008.

Methylation of a conserved intronic CpG island of mouse SF-1 is associated with cell-specific

expression of SF-1 in a culture system but not with tissue-specific expression.

Biochem Biophys Res Commun. 369,862-867.

72

73

74

Ikuyama S, Gu JQ, Nishimura J. (2008, 6/15-6/18)

PycnogenolR, an extract from the bark of maritime pine, suppresses the expression of Toll-like receptor

4-mediated ADRP expression in macrophages.

90th Annual Meeting of The Endocrine Society, San Francisco, USA.

Gondo S, Tanaka T, Gondo H, Okabe T, Morinaga H, Nomura M, Takayanagi R, Nawata H,

Yanase

T . (2008,11/9)

Adipose tissue-derived and bone marrow-derived mesenchymal cells develop into different lineage of

steroidogenic cells by forced expression of SF-1

The 2nd

Global COE International Symposium joint with the 18th

Hot Spring Harbor Symposium of

Medical Institute of Bioregulation, Kyushu University, Fukuoka.

75

76

77

Division of Neurofunctional Genomics

DNA

DNA

DNA

jun fos

20 4

Hand in Hand

8 1 11 1

DNA RNA

78

DNA

MutT MTH1 ATP

ITP ITPase

ATP ITP

RS21-C6

RS21-C6 ITP ATP RS21-C6

dCTP dATP dTTP

kcat/Km 3.11x104

4.49x103

1.87x103

dGTP

5-I-dCTP kcat/Km dCTP 8 RS21-C6

RS21-C6

RS21-C6 dCTP

dTTP de novo dCMP

RS21-C6 dCTP

DNA DNA DNA

2 AP APEX2 3’-5’

3’- AP

APEX2 PCNA proliferating cell nuclear antigen

S APEX2 APEX2

APEX2

1/5 CD4+/CD8

+,

CD4-/CD8

+, CD4

+/CD8

- T 1/5 CD4

-/CD8

-

T

79

APEX2 microarray

APEX2 APEX2

CD4-/CD8

- T

CD4+/CD8

+ T CD4

+CD8

+

T

APEX2 T

T T

APEX2

DNA

ATM/ATR CHK1/CHK2 pRb

DNA E2F p53

APEX2 p53 Ser23 E2F

p53 DNA APEX2

DNA H2AX

APEX2 DNA

APEX2

3’ DNA

DNA

APEX2 DNA

APEX2

APEX2 DNA

MTH1

DNA RNA

DNA 8-oxoguanine (8-oxoG) MTH1

MTH1

MTH1 (hMTH1)

(hMTH1-Tg) 3-

3-NP

80

3-NP

3-NP

hMTH1-Tg 3-NP

55 5 hMTH1-Tg

20 80

hMTH1-Tg 30 8-oxoG

3-NP

hMTH1-Tg 8-oxoG

3-NP

8-oxo-dGTP DNA

fosB fosB fosB

mRNA fosB mRNA FosB

fosB mRNA FosB 2 FosB FosB

FosB AP-1 FosB

C-

2 FosB

FosB/ 2 FosB ES fosBd/d

fosB fosB-null ES microarray

fosB-null ES

44 (0.83%) fosBd/d

ES FosB

10 2 FosB fosBd/d

ES

221 (4.18%) 46 (0.87%)

fosB-null ES fosBd/d

ES FosB/ 2 FosB

200 19 FosB/ 2 FosB

fosBd/d

ES

laminin ( 1, 1, 1) collagen type IV ( 1, 2)

Akt1 GATA6

Thbs1, Tgfb1, Tgfb1i1 TGF- 1 fosB-null

ES fosBd/d

ES

81

fosBd/d

ES

fosB-null ES FosB

fosBFN/FN

ES Tgfb1i1

mRNA

FosB TGF- 1

FosB/ 2 FosB TGF- 1 FosB

1. Nonaka, M., Tsuchimoto, D., Sakumi, K. and Nakabeppu, Y. (2009).

Mouse RS21-C6 is a mammalian 2’-deoxycytidine 5’-triphosphate pyrophosphohydrolase that prefers

5-iodocytosine.

FEBS J, 276, 1654-1666.

2. Kajitani, K., Nomaru, H., Ifuku, M., Yutsudo, N., Dan, Y., Miura, T., Tsuchimoto, D., Sakumi, K., Kadoya, T.,

Horie, H., Poirier, F., Noda, M. and Nakabeppu, Y. (2009).

Galectin-1 promotes basal and kainate-induced proliferation of neural progenitors in the dentate gyrus of adult

mouse hippocampus.

Cell Death Differ, 16, 417-427.

3. Nakane, H., Hirota, S., Brooks, P.J., Nakabeppu, Y., Nakatsu, Y., Nishimune, Y., Iino, A. and Tanaka, K. (2008).

Impaired spermatogenesis and elevated spontaneous tumorigenesis in xeroderma pigmentosum group A gene

(Xpa)-deficient mice.

DNA Repair, 7, 1938-1950.

4. De Luca, G., Russo, M.T., Degan, P., Tiveron, C., Zijno, A., Meccia, E., Ventura, I., Mattei, E., Nakabeppu, Y.,

Crescenzi, M., Pèpponi, R., Pzzola, A., Popoli, P. and Bignami, M. (2008).

A Role for Oxidized DNA Precursors in Huntington's Disease-Like Striatal Neurodegeneration.

PLoS Genet, 4, e1000266.

5. Ohnishi, Y.N., Sakumi, K., Yamazaki, K., Ohnishi, Y.H., Miura, T., Tominaga, Y. and Nakabeppu, Y. (2008).

Antagonistic regulation of cell-matrix adhesion by FosB and FosB/ 2 FosB encoded by alternatively spliced

forms of fosB transcripts.

82

Mol Biol Cell, 19, 4717-4729.

6. Dan, Y., Ohta, Y., Tsuchimoto, D., Ohno, M., Ide, Y., Sami, M., Kanda, T., Sakumi, K. and Nakabeppu, Y.

(2008)

Altered gene expression profiles and higher frequency of spontaneous DNA strand breaks in APEX2-null

thymus.

DNA Repair, 7, 1437-1454.

7. Yanaru-Fujisawa, R., Matsumoto, T., Ushijima, Y., Esaki, M., Hirahashi, M., Gushima, M., Yao, T., Nakabeppu,

Y. and Iida, M. (2008).

Genomic and functional analyses of MUTYH in Japanese patients with adenomatous polyposis.

Clin Genet, 73, 545-553.

8. Yamamoto, S., Tanaka, K., Sakimura, R., Okada, T., Nakamura, T., Li, Y., Takasaki, M., Nakabeppu, Y. and

Iwamoto, Y. (2008).

Suberoylanilide hydroxamic acid (SAHA) induces apoptosis or autophagy-associated cell death in

chondrosarcoma cell lines.

Anticancer Res, 28, 1585-1591.

1. Ohno, M., Oka, S. and Nakabeppu, Y. (2009).

Quantitative analysis of oxidized guanine, 8-oxoguanine, in mitochondrial DNA by immunofluorescence

method.

Methods Mol Biol, (in press).

2. Oka, S., Ohno, M. and Nakabeppu, Y. (2009).

Characterization of cell death pathway triggered by an oxidative base lesion, 8-oxoguanine selectively

accumulated in mitochondrial DNA.

Methods Mol Biol, (in press).

3. (2008).

DNA

26 9 1376-1379.

1. Yusaku Nakabeppu (2009, 3/27-3/28).

Oxidative damage in brain genome and neuroprotection.

83

The 11th Meeting of Hirosaki International Forum of Medical Science Emerging Frontiers in Brain Research

-Crossroads of metabolic regulation, stress response and disease, Hirosaki.

2. (2009, 3/23).

170 20

3. Yusaku Nakabeppu (2009, 2/15-2/16).

MUTYH, a molecular switch for programmed cell death under oxidative stress-friend or foe?

The 3rd Global COE International Symposium on Stem Cells and Regenerative Medicine, Singapore.

4. Yusaku Nakabeppu (2009, 1/31-2/1).

Oxidative genomic damage in brain and neuroprotection.

The Joint Symposium of the 4th International Symposium of Institutes Network and Osaka University Global

COE (Frontier Biomedical Science Underlying Organelle Network Biology) Symposium, Osaka.

5. (2008, 12/18-12/20).

3- 8- MUTYH

MTH1 OGG1

8

6. (2008, 12/18-12/20).

Overview of programmed cell death and oxidative stress

8

7. (2008, 12/16-12/17).

3

DNA

8. Nomaru, H., Kajitani, K., Ifuku, M., Yutsudo, N., Dan, Y., Miura, T., Tsuchimoto, D., Sakumi, K., Kadoya, T.,

Horie, H., Poirier, F., Noda, M. and Nakabeppu, Y. (2009, 12/10-12/12).

Galectin-1 promotes basal and kainate-induced proliferation of neural progenitors in the dentate gyrus of adult

mouse hippocampus.

Berlin Brain Days 2008, Berlin, Germany.

9. (2008, 12/9-12/12).

2-OH-ATP

BMB2008 31 81

10. (2008, 12/9-12/12).

84

OGG1/MTH1/MUTYH

BMB2008 31 81

11. (2008, 12/9-12/12).

ITPBP2

BMB2008 31 81

12. (2008, 12/9-12/12).

Ogg1, Mth1, Mutyh 3

BMB2008 31 81

13. (2008, 12/9-12/12).

cAMP phosphodiesterase

BMB2008 31 81

14. (2008, 12/9-12/12).

DNA 8-oxoguanine

BMB2008 31 81

15. Abolhassani Nona, Kunihiko Sakumi, Mizuki Ohno, Daisuke Tsuchimoto, Mehrdad Behmanesh, Yusaku

Nakabeppu (2008, 12/9-12/12).

Novel pathway for hydrolysis of inosine nucleotides detected in immortalized ITPA-null mouse embryo

fibroblasts.

BMB2008 31 81

16. Mizuki Ohno and Yusaku Nakabeppu (2008, 12/4-12/5).

8-Oxoguanine is a major cause for the genome instability and diversity through enhancing the somatic and

meiotic recombination.

37

17. Zahra Sabouri, Il-mi Okazaki, Reiko Shinkura, Daisuke Tsuchimoto, Yusaku Nakabeppu, Tasku Honjo (2008,

12/1-12/3).

Class Switch Recombination and Somatic Hypermutation in Ape2-deficient Mice

38

18. Yoshinori N. Ohnishi, Yoko H. Ohnishi, Ami Graham, Christopher Cowan, Cathy Steffen, Shari Birnbaum,

Yusaku Nakabeppu, Eric J. Nestler (2008/11/15-11/20).

The N-terminal domain of FosB is functional in behavioral responses.

The 38th annual meeting of the Society for Neuroscience, Washington, DC, USA.

85

19. Zijing Sheng, Sugako Oka and Yusaku Nakabeppu (2008, 11/7-11/9).

The mitochondrial toxin, 3-nitropropionic acid induces MUTYH-dependent striatal neurodegeneration with

accumulation of 8-oxoguanine which is effectively suppressed by OGG1 and MTH1.

The 5th ASMRM and Chinese Mit’2008, Tianjin, China.

20. (2008, 10/28-10/30).

MUTYH DNA 8- 2

67

21. Mizuki Ohno and Yusaku Nakabeppu (2008, 10/27-10/30).

8-Oxoguanine, a major form of spontaneously oxidized guanine base, promotes genome diversity through

enhancing chromosome recombination.

The 6th 3R (Replication, recombination, repair) Symposim, Kakegawa.

22. (2008, 9/3-9/5).

8-

80

23. (2008, 9/3-9/5).

Ogg1/Mth1/Mutyh

80

24. (2008, 8/2-8/3).

27

25. Mizuki Ohno, Masato Furuichi, Kunihiko Sakumi, Yusaku Nakabeppu (2008, 7/12-7/17).

8-Oxoguanine promotes genetic diversity through enhancing meiotic recombination,

XX International Congress of Genetics, Berlin, Germany.

26. Noriko Yutsudo, Yoko Honda-Ohnishi, Yoshinori Ohnishi, Kunihiko Sakumi, Yusaku Nakabeppu (2008,

7/9-7/11).

FosB promotes neurogensis in the dentate gyrus of mouse hippocampus

31

27. Sheng Zijing, Hidetaka Yamada, Yusaku Nakabeppu (2008, 7/9-7/11).

OGG1 and MTH1 effectively suppress accumulation of 8-oxoguanine in striatal medium spiny neurons and

their degeneration induced by mitochondrial toxin, 3-nitropropionic acid.

31

86

28. Hiroko Nomaru, Kosuke Kajitani, Masataka Ifuku, Toshihiko Kadoya, Hidenori Horie, Françoise Poirier,

Mami Noda, Kunihiko Sakumi, Yusaku Nakabeppu (2008, 7/9-7/11).

Galectin-1 expressed in astrocytes promotes neurogenesis in the mouse hippocampus after brain damage caused

by excitotoxicity.

31

29. (2008, 6/19-6/20).

61

30. Junji Ichikawa, Daisuke Tsuchimoto, Sugako Oka, Mizuki Ohno, Kunihiko Sakumi, Yusaku Nakabeppu (2008,

6/11-6/14).

Oxidation of mitochondrial deoxynucleotide pools induces mitochondrial degeneration and cell death.

The 7th European Meeting on Mitochondrial Pathology, Stockholm, Sweden.

31. Sugako Oka, Mizuki Ohno, Daisuke Tsuchimoto, Kunihiko Sakumi, Masato Furuichi and Yusaku Nakabeppu

(2008, 6/11-6/14).

Two distinct pathways of cell death triggered by oxidative damage to nuclear and mitochondrial DNAs.

The 7th European Meeting on Mitochondrial Pathology, Stockholm, Sweden.

32. (2008, 5/21-5/22).

8-

2008 9 15 31

33. (2008, 5/22-5/23).

Msh2

2008 9 15 31

34. (2008, 5/22-5/23).

DNA

2008 9 15 31