2007 Fiscal Year Final Research Report Summary
Redox regulation of inflammation and carcinogenesis mediated by NF-κB/IKKβ and dual-specificity phosphatase
| Project/Area Number |
18570136
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Functional biochemistry
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| Research Institution | Hiroshima University |
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Principal Investigator |
KAMATA Hideaki Hiroshima University, Graduate School of Biomedical Sciences, Associate Professor (10233925)
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| Project Period (FY) |
2006 – 2007
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| Keywords | REDOX / CANCER / INFLAMMATION / IKKβ / OXIDATIVE STRES / NF-κB / MAP KINASE PHOSPHATASE |
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| Research Abstract |
A major link between inflammation and carcinogenesis depends on several cellular signaling systems including the ilacp/NF-кB pathway and the MAP kinase cascade. Especially, tumor necrosis factor (TNF・), which activates NF-кB through IKKβ and JNK, plays an important role both inflammation and carcinogenesis. To reveal how these signaling systems regulate inf lammation and carci nogenesis, we investigated cellular responses of mutant cells deficlent in NF-кB activation. TNF・induced reactive oxygen species (ROS) production in these mutant cells and lead cell death. TNF・-mediated cell death is thought to be profoundly involved in carcinogenesis in liver. Cell death is medicated by inactivation of several tyrosine phosphatases of which active site is redox-sensitive cysteine residue including MAP kinase phosphatases. Inactivation of MKPs leads the sustained JNK activation and caspase activation. Interestingly, although ROS oxidize PTEN, the down stream kinase Akt of which activation can promote cell survival is degraded by caspases. Thus, TNF・induces cell death by inactivation of MKP and by Akt degradation mediated by oxidative stress.
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[Journal Article] Hepatic overexpression of a doninant negative form of raptor enhances Akt phosphorylation and restores insulin sensitivity in K/KAy mice.2008
Author(s)
Yuko Koketsu, Hideyuki Sakoda, Midori Fujishiro, Akifurni Kushiyama, Yasushi Fukushima, Hiraku Ono, Motonobu Anai, Takako Kikuchi, Takeshi Fukuda, Hideaki Kamata, Nanao Hor ike, Yasunobu Uchijima, Hiroki Kurihara, Tomoichiro Asano
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Journal Title
Am J Physiol Endocrinol Metab. 294(4)
Pages: E719-25
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Regulation of gut-derived resistin-like molecule beta expression by nutrients.2008
Author(s)
Junko Fujio, Akifumi Kushiyama, Hideyuki Sakoda, Midori Fujishiro, Takehide Ogihara, Yasushi Fukushima, Motonobu Anai, Nanao Hor ike, Hideaki Kamata, Yasunobu Uchijima, Hiroki Kurihara, Tomoichiro Asano
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Journal Title
Diabetes Res Clin Pract. 79
Pages: 2-10
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Carboxyl-terminal modulator protein (ctmp) induces akt phosphorylation and activation, thereby enhancing anti-apoptotic, glycogen synthetic and glucose uptake pathways.2007
Author(s)
Hiraku Ono, Hideyuki Sakoda, Midori Fujishiro, Motonobu Anai, Akifumi Kushiyama, Yasushi Fukushima, Hideki Katagiri, Takehide Ogihara, Yoshitomo Oka, Hideaki Kamata, Nanao Horike, Yasunobu Uchijima, Hiroki Kurihara, Tomoichiro Asano
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Journal Title
Am J Physiol Cell Physiol. 293(5)
Pages: C1576-85
Description
「研究成果報告書概要(欧文)」より
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