Regulation of apolipoprotein A-I gene expression by ascorbic acid in scurvy-prone ODS-od/od rats.

抗坏血酸对易患坏血病的 ODS-od/od 大鼠中载脂蛋白 A-I 基因表达的调节。

• 批准号: 05660136
• 负责人: HORIO Fumihiko
• 金额: $ 1.41万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 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/en/grant/KAKENHI-PROJECT-05660136/
• 关键词: Ascorbic acid; Apolipoprotein A-I; Atherosclerosis; Vitamin C

Apolipoprotein A-I (Apo A-I) is a major apolipoprotein of serum high density lipoprotein (HDL) , which transports cholesterol from peripheral tissues to liver. We observed that apo A-I in serum HDL was decreased in ascorbic acid (AsA) deficiency in scurvy-prone ODS-od/od rats. In this study, we examined the mechanism how AsA deficiency causes a low level Apo A-I in serum.The Apo A-I mRNA level in the liver but not in the small intestine was decreased (50%) in AsA-deficient group compared to in the control group. As AsA deficiency did not affect the transcription rate of Apo A-I gene, AsA might be required to stabilize Apo A-I mRNA.Moreover, a lower level of albumin mRNA,a higher level of haptoglobin mRNA and a higher level of 1-acid glycoprotein mRNA in the liver was observed in ascorbic acid-deficienct rats compared to in the control rats. These changes in hepatic levels of mRNA including Apo A-I mRNA are also observed in acute phase or inflammation. At present, we are measuring the serum levels of interleukin-6, which is a major cytokine secreted in acute phase and inflammation, in ascorbic acid deficiency.

载脂蛋白A-I（ApoA-I）是血清高密度脂蛋白（HDL）的主要载脂蛋白，负责将胆固醇从外周组织转运至肝脏。我们观察到抗坏血酸（阿萨）缺乏可使易患坏血病的ODS-od/od大鼠血清HDL中apo A-I降低。在本研究中，我们探讨了阿萨缺乏导致血清中Apo A-I水平降低的机制，发现与对照组相比，AsA缺乏组肝脏中的Apo A-I mRNA水平降低了50%，而小肠中的Apo A-I mRNA水平没有降低。由于阿萨缺乏不影响Apo A-I基因的转录速率，因此可能需要阿萨来稳定Apo A-I mRNA，而且与对照组相比，抗坏血酸缺乏大鼠肝脏中白蛋白mRNA水平降低，结合珠蛋白mRNA水平升高，1-酸性糖蛋白mRNA水平升高。在急性期或炎症中也观察到肝脏mRNA（包括Apo A-I mRNA）水平的这些变化。目前，我们正在测定抗坏血酸缺乏时血清中白细胞介素-6的水平，白细胞介素-6是急性期和炎症中分泌的主要细胞因子。

项目成果

Ikeda, S.: "Ascorbate deficiency decreases hepatic apolipoprotein A-I mRNA in a scurvy-prone rat (genotype ODS-od/od)." Biochem.J.(submitted.).

Ikeda, S.：“抗坏血酸缺乏会降低坏血病倾向大鼠（基因型 ODS-od/od）的肝载脂蛋白 A-I mRNA。”

Uchida,K.: "Acute nephrotoxicity of a carcinogenic iron chelate selective inhibition of a proteolytic conversion of 2u-globulin to the kidney fatty acid-binding protein." FEBS Letters. 357. 165-167 (1995)

Uchida,K.：“致癌铁螯合物的急性肾毒性选择性抑制 2u-球蛋白向肾脂肪酸结合蛋白的蛋白水解转化。”

Uchida,K.: "Acute nephrotoxicity of a carcinogenic iron chelate selective inhibition of a proteolytic conversion of 2n-globulin to the Kidney fatty acid-binding protein." FEBS Letters. 357. 165-167 (1995)

Uchida,K.：“致癌铁螯合物的急性肾毒性选择性抑制 2n-球蛋白向肾脂肪酸结合蛋白的蛋白水解转化。”

Ikeda,S.: "Ascorbate deficiency decreases hepatic apolopoprotein A-I mRNA in a scurvy-prone rat(genotype ODS-od/od)." Biochem.J,.submitted.

Ikeda,S.：“抗坏血酸缺乏会降低坏血病倾向大鼠（基因型 ODS-od/od）的肝载脂蛋白 A-I mRNA。”