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Studies n Functional Roles of Fatty Acid-Binding Proteins

脂肪酸结合蛋白的功能作用研究

基本信息

批准号：
05044154
负责人：
ONO Teruo
金额：
$ 4.16万
依托单位：
Niigata University
依托单位国家：
日本
项目类别：
Grant-in-Aid for international Scientific Research
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1994
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-05044154/
关键词：
Fatty Acid-Binding Protein (FABP)H-FABP C-FABP I-FABP I-15P Diabetes Mellitus Ischaemic Intestinal Diseases Fluorescent Fatty Acid L-FABP 心筋梗塞脂肪酸ステロイド産生臓器

项目摘要

We have studied on functional roles of cellular fatty acid-binding proteins (FABPs) in the following aspects.(1) Transfer mechanism of FABP bound-fatty acids to membranes :Using an in vitro fluorescence energy transfer assay, we presented the evidence that H-FABP and L-FABP bound-fatty acids are transferred to membranes through different mechanism. Fatty acids from H-FABP was transferred by collisional interaction, while the rate limiting step from L-FABP was the dissociation rate of fatty acids to aqueous medium.(2) A new FABP (C-FABP) from rat skin :We have purified a new subtype of H-FABP from rat skin and cloned this protein. The deduced amino acid sequence of the cDNA clone comprises residues yielding a molecular mass for the polypeptide of 15 kDa and the primary structure is homologus to H-FABP family proteins. Interestingly, it has six cysteines and two intramolecular disulfide bridges are present. This is the first presentation of disulfide formed protein among FABPs superfamily. Three dimensional structure of this new type of FABP may afford a new sight of functional roles of this protein family in the future.(3) Regulatory mechanism of H-FABP expression in aorta :We have analyzed the H-FABP expression in diabetic rat aorta and provided the evidence that the H-FABP gene in aorta is specifically and uniquely regulated by insulin when compared to the H-FABP expression in heart tissue. Insulin regulated H-FABP expression in aorta may be involved in diabetic complications of blood vessels.(4) Clinical application of I-FABP :Taking the advantage of specific expression of I-FABP limited in intestinal tissue, we have applied the I-FABP as a diagnostic tool. We have showed that the I-FABP is released into the circulation in the acute phase of intestinal ischaemia. Accordingly, the measurement of I-FABP in serum can be used in establishing the diagnosis of ischaemic intestinal diseases.

本论文从以下几个方面对细胞脂肪酸结合蛋白的功能进行了研究。(1)FABP结合脂肪酸向细胞膜的转移机制：通过体外荧光能量转移实验，证明H-FABP和L-FABP结合脂肪酸通过不同的转移机制向细胞膜转移。H-FABP的脂肪酸通过碰撞相互作用转移，而L-FABP的速率限制步骤是脂肪酸向水介质的解离速率。(2)一种新的大鼠皮肤脂肪酸结合蛋白（C-FABP）：我们从大鼠皮肤中纯化了一种新的H-FABP亚型，并克隆了该蛋白。cDNA克隆的推导的氨基酸序列包含产生15 kDa的多肽分子量的残基，并且一级结构与H-FABP家族蛋白同源。有趣的是，它有六个半胱氨酸和两个分子内二硫键。这是FABPs超家族中首次出现二硫键形成蛋白。这种新型FABP的三维结构为进一步研究该蛋白家族的功能提供了新的视角。(3)主动脉H-FABP表达的调控机制：我们分析了糖尿病大鼠主动脉H-FABP的表达，并提供了证据表明，主动脉H-FABP基因是特异性和独特的调节胰岛素相比，心脏组织H-FABP的表达。胰岛素调节主动脉H-FABP表达可能参与糖尿病血管并发症的发生。(4)I-FABP的临床应用：利用I-FABP在肠组织中特异性表达的特点，将其作为诊断工具。我们已经表明，I-FABP在肠缺血的急性期释放到循环中。因此，血清中I-FABP的测定可用于建立缺血性肠道疾病的诊断。