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Progress in researches about focal adhesion kinase in gastrointestinal tract

World Journal of Gastroenterology 2009年第47期15卷 5916-5923页

作者： Hui Fang Hao Yoshio Naomoto Xiao-Hong Bao Nobuyuki Watanabe Kazufumi Sakurama Kazuhiro Noma yasuko tomono Takuya Fukazawa Yasuhiro Shirakawa Tomoki Yamatsuji Junji Matsuoka Munenori Takaoka Department of Gastroenterological Surgery Transplantation and Surgical Oncology Graduate School of Medicine Dentistry and Pharmaceutical Sciences Okayama University Okayama 700-8558 Japan Shigei Medical Research Institute Okayama 700-8558 Japan

Focal adhesion kinase(FAK)is a 125-kDa non-receptor protein *** factors or the clustering of integrins facilitate the rapid phosphorylation of FAK at Tyr-397 and this in turn recruits Src-family protein tyrosine kinases,resulting in the phosphorylation of Tyr-576 and Tyr-577 in the FAK activation loop and full catalytic FAK *** plays a critical role in the biological processes of normal and cancer cells including the gastrointestinal *** also plays an important role in the restitution,cell survival and apoptosis and carcinogenesis of the gastrointestinal *** is over-expressed in cancer cells and its over-expression and elevated activities are associated with motility and invasion of cancer *** has been proposed as a potential target in cancer *** molecule inhibitors effectively inhibit the kinase activity of FAK and show a potent inhibitory effect for the proliferation and migration of tumor cells,indicating a high potential for application in cancer therapy.

关键词： Focal adhesion kinase Restitution Survival and apoptosis Cancer Inhibitor

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Glutamine depletion induces murine neonatal melena with increased apoptosis of the intestinal epithelium

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World Journal of Gastroenterology 2011年第6期17卷 717-726页

作者： Takayuki Motoki Yoshio Naomoto Junji Hoshiba Yasuhiro Shirakawa Tomoki Yamatsuji Junji Matsuoka Munenori Takaoka yasuko tomono Yasuhiro Fujiwara Hiroshi Tsuchita Mehmet Gunduz Hitoshi Nagatsuka Noriaki Tanaka Toshiyoshi Fujiwara Department of Gastroenterological Surgery Transplantand Surgical OncologyGraduate School of MedicineDentistryand Pharmaceutical SciencesOkayama University Department of General Surgery Kawasaki Medical School Kawasaki Hospital Division of Molecular and Cell Biology Shigei Medical Research Institute Department of Animal Resources Advanced Science Research CenterOkayama University Food Technology Research Institute Meiji Dairies Corporation Department of Oral Pathology and Medicine Graduate School of MedicineDentistryand Pharmaceutical SciencesOkayama University

AIM:To investigate the possible biological outcome and effect of glutamine depletion in neonatal mice and rodent intestinal epithelial ***:We developed three kinds of artificial milk with different amounts of glutamine;Complete amino acid milk (CAM),which is based on maternal mouse milk,glutamine-depleted milk (GDM),and glutaminerich milk (GRM).GRM contains three-fold more glutamine than ***-seven newborn mice were divided into three groups and were fed with either of CAM,GDM,or GRM via a recently improved nipple-bottle system for seven *** the feeding period,the mice were subjected to macroscopic and microscopic observations by immunohistochemistry for 5-bromo-2'deoxyuridine (BrdU) and Ki-67 as markers of cell proliferation,and for cleaved-caspase-3 as a marker of ***,IEC6 rat intestinal epithelial cells were cultured in different concentrations of glutamine and were subject to a 4-[3-(4-iodophenyl)-2-(4-nitrophenyl)2H-5-tetrazolio]-1,3-benzene disulfonate cell proliferation assay,flow cytometry,and western blotting to examine the biological effect of glutamine on cell growth and ***:During the feeding period,we found colonic hemorrhage in six of 28 GDM-fed mice (21.4%),but not in the GRM-fed mice,with no differences in body weight gain between each *** examination showed destruction of microvilli and the disappearance of glycocalyx of the intestinal wall in the colon epithelial tissues taken from GDM-fed *** of GDM reduced BrdU incorporation (the average percentage of BrdU-positive staining;GRM:13.8%,CAM:10.7%,GDM:1.14%,GRM vs GDM:P < 0.001,CAM vs GDM:P < 0.001) and Ki-67 labeling index (the average percentage of Ki67-positive staining;GRM:24.5%,CAM:22.4% GDM:19.4%,GRM vs GDM:P=0.001,CAM vs GDM:P =0.049),suggesting that glutamine depletion inhibited cell proliferation of intestinal epithelial *** deprivation further caused the deformation of the nuclear membrane and the plasma m

关键词： Glutamine Newborn mice Artificial milk Melena Intestinal epithelial cells Apoptosis

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