Research on regulation of absorption and metabolism of sterols by ABC transporters

ABC转运蛋白对甾醇吸收代谢的调控研究

• 批准号: 14560102
• 负责人: IKEDA Ikuo
• 金额: $ 2.69万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14560102/
• 关键词: ABCG5; ABCG8; SHRSP rats; plant sterols; absorption; LXR; LXR agonist; Liver X receptor; コレステロール; Liver X receptorアゴニスト; 高植物ステロール血症; WKYラット

We found that SHRSP rats, which deposit plant sterols in their body, have a point mutation on ATP binding cassette transporter (ABC)G 5. ABCG5 and G8 form a heterodimer and have a function to excrete cholesterol and plant sterols from intestine and liver. Since the function of ABCG5 and G8 is insufficient in SHRSP rats, plant sterols may be deposited in their body. Expression of ABCG5 and G8 is regulated by liver X receptor. In the next study, LXR agonist was fed to SHRSP and normal rats together with plant sterols. Although expression of ABCG5 and G8 in the intestine of SHRSP and normal rats was increased by the feeding of LXR agonist, plant sterols in the liver of SHRSP rats were hardly reduced. In contrast, deposition of plant sterols in the liver of normal rats was reduced. The results strongly suggest that SHRSP rats can hardly excrete plant sterols from their body. Expression of ABCG5 and G8 in the liver was not stimulated by the feeding of LXR agonist in SHRSP rats. This may be one of the reasons by which plant sterols in the liver of SHRSP rats was not reduced by the feeding of LXR agonist.

我们发现，体内存款植物甾醇的SHRSP大鼠在ATP结合盒转运体（ABC）G 5上存在点突变。ABCG 5和G8形成异二聚体，并具有从肠和肝排泄胆固醇和植物甾醇的功能。SHRSP大鼠ABCG 5和G8功能不全，植物甾醇可能在其体内沉积。ABCG5和G8的表达受肝X受体的调节。在接下来的研究中，LXR激动剂与植物甾醇一起喂养SHRSP和正常大鼠。LXR激动剂可增加SHRSP和正常大鼠肠道ABCG 5和G8的表达，但对SHRSP大鼠肝脏中植物甾醇的含量几乎没有影响。相反，正常大鼠肝脏中植物甾醇的沉积减少。结果表明，SHRSP大鼠几乎不能从体内排出植物甾醇。LXR激动剂对SHRSP大鼠肝脏ABCG 5和G8的表达无明显刺激作用。这可能是LXR激动剂不能降低SHRSP大鼠肝脏中植物甾醇含量的原因之一。

项目成果

H.Yu et al.: "The rat STSL locus : characterization, chromosomal assignment, and genetic variations in sitosterolemic hypertensive rats"BMC Cardiovascular Disorders. 3. 4 (2003)

H.Yu 等人：“大鼠 STSL 基因座：谷甾醇血症高血压大鼠的特征、染色体分配和遗传变异”BMC 心血管疾病。

HongWei Yu, Bhaewati Pandit, Eric Klett, Mi-Hye Lee, Kangmo Lu, Khalil Helou, Ikuo Ikeda, Nami Egashira, Masao Sato, Richard Klein, Ashok Batta, Gerald Salen, Shailendra B.Patel: "The rat STSL locus : characterization, chromosomal assignment, genetic vari

HongWei Yu、Bhaewati Pandit、Eric Klett、Mi-Hye Lee、Kangmo Lu、Khalil Helou、Ikuo Ikeda、Nami Egashira、Masao Sato、Richard Klein、Ashok Batta、Gerald Salen、Shailendra B.Patel：“大鼠 STSL 基因座：表征