Analysis of Novel Cellular Functions of Fatty Acid Binding Proteins

脂肪酸结合蛋白的新细胞功能分析

• 批准号: 18390056
• 负责人: KONDO Hisatake
• 金额: $ 10.56万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18390056/
• 关键词: Brain-type FABP; Epidermal-type FABP; Fear and Anxiety,; Schizophrenia; Dendritic cells; IL-12,; 脂肪酸結合タンパク; 脾臓樹状細胞、; 不安・恐怖記憶、; 脳型(B-)、表皮型(E-); 遺伝子欠損マウス、; IL-12産生制御; 脂肪酸; マウス; 樹状細胞; マクロファージ; PPAR

Mutant mice for epidermal (E)-type and brain (B)-type fatty acid binding proteins (FABPs) were successfully generated as the first attempts in the world by us and they were fully analyzed throughout the project. The mutants for B-FABP exhibited enhanced anxiety and increased fear memory in the behavioral examination, while they decreased the content of docosahezaenoic acid (DHA) in the brain only at neonatal period without any histological changes in the brain at adult or neonate stages. The B-FABP mutants also showed decreased prepulse inhibition whose deficits are a biological marker for schizophrenia. All the data suggest a novel and crucial role of B-FABP in the pathology of schizophrenia. The mutants for E-FABP exhibited a lower mortality rate in the peritonitis by infection of Salmonella as compared with the wild counterpart. By in vitro analysis, dendritic cells isolated from the mutant spleen showed enhanced production of IL-12p70 in response to appropriate stimuli and higher levels of phosphorylated forms of p38 mitogen-activated protein kinase and IkBa after LPS stimulation as compared with the wild. These results suggest that the lower mortality rate in the peritonitis of the mutants was due to the possible role of E-FABP as a negative regulator of IL-12 production in the dendritic cells.

我们在世界上首次尝试成功地产生了表皮（E）型和脑（B）型脂肪酸结合蛋白（FABPs）的突变小鼠，并在整个项目中对其进行了全面分析。B-FABP突变体在行为学检查中表现出焦虑增强和恐惧记忆增加，而它们仅在新生期降低脑中二十二碳六烯酸（DHA）的含量，而在成年或新生期脑中没有任何组织学变化。B-FABP突变体也表现出减少的前脉冲抑制，其缺陷是精神分裂症的生物标志物。所有的数据表明，B-FABP在精神分裂症的病理学中的一个新的和关键的作用。与野生型相比，E-FABP的突变体在沙门氏菌感染的腹膜炎中表现出较低的死亡率。通过体外分析，与野生型相比，从突变体脾脏中分离的树突状细胞显示出响应于适当刺激的IL-12 p70的产生增强，以及LPS刺激后p38促分裂原活化蛋白激酶和IkBa的磷酸化形式的水平更高。这些结果表明，较低的死亡率在腹膜炎的突变体是由于E-FABP的树突状细胞中的IL-12生产的负调节剂的可能作用。

项目成果

'Cellular Lipid Binding Proteins'in Mol Cell Biochem special issues vol 299

Mol Cell Biochem 特刊第 299 卷中的“细胞脂质结合蛋白”

• 发表时间: 2007
• 作者: Kondo H;Owada Y;Glatz JF
• 通讯作者: Glatz JF

Enhanced expression of adipocyte-type fatty acid binding protein in murine lymphocytes in response to dexamethasone treatment

• DOI: 10.1007/s11010-005-9050-1
• 发表时间: 2007-05-01
• 期刊: MOLECULAR AND CELLULAR BIOCHEMISTRY
• 影响因子: 4.3
• 作者: Abdelwahab, Soha Abdelkawi;Owada, Yuji;Kondo, Hisatake
• 通讯作者: Kondo, Hisatake

Expression of E-FABP in bone marrow- derived mast cells and regulation mechanism of TNP-a production

骨髓源性肥大细胞中E-FABP的表达及TNP-a产生的调控机制

• 发表时间: 2007
• 作者: Owada Y;Kondo H ed. al.
• 通讯作者: Kondo H ed. al.

‘Cellular Lipid Binding Proteins' in Mol Cell Biochem special issues vol 299

Mol Cell Biochem 特刊第 299 卷中的“细胞脂质结合蛋白”

• 发表时间: 2007
• 作者: Kondo H;Owada Y;Glatz JF
• 通讯作者: Glatz JF

Fabp7 maps to a quantitative trait locus for a schizophrenia endophenotype.

• DOI: 10.1371/journal.pbio.0050297
• 发表时间: 2007-11
• 期刊: PLOS BIOLOGY
• 影响因子: 9.8
• 作者: Watanabe, Akiko;Toyota, Tomoko;Owada, Yuji;Hayashi, Takeshi;Iwayama, Yoshimi;Matsumata, Miho;Ishitsuka, Yuichi;Nakaya, Akihiro;Maekawa, Motoko;Ohnishi, Tetsuo;Arai, Ryoichi;Sakurai, Katsuyasu;Yamada, Kazuo;Kondo, Hisatake;Hashimoto, Kenji;Osumi, Noriko;Yoshikawa, Takeo
• 通讯作者: Yoshikawa, Takeo