Acyl-coenzyme A:Cholesterol acyltransferase-2 (ACAT-2) is responsible for elevated intestinal ACAT activity in diabetic rats
Acyl-coenzyme A:Cholesterol acyltransferase-2 (ACAT-2) is responsible for elevated intestinal ACAT activity in diabetic rats
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DOI：
10.1161/01.atv.0000137976.88533.13
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发表时间：
2004-09-01
影响因子：
8.7
通讯作者：
Horiuchi, S
中科院分区：
文献类型：
--
作者：
Hori, M;Satoh, M;Horiuchi, S
糖尿病诱导的血脂异常见于链脲佐菌素诱导的糖尿病大鼠。这部分是由肠酰基辅酶A：胆固醇酰基转移酶（ACAT）活性升高引起的。由于两个ACAT同工酶（ACAT-1和ACAT-2）被确定，在本研究中，我们确定ACAT同工酶参与升高的肠道ACAT活性在糖尿病rates.Methods和Results-We克隆了大鼠ACAT-2的全长cDNA。其在ACAT缺陷型AC 29细胞中的过表达表明，ACAT活性源自克隆的cDNA，并且大鼠ACAT-2的45-kDa蛋白质与抗人ACAT-2抗体交叉反应。大鼠ACAT-2 mRNA的组织分布显示其仅在肝脏和小肠表达。抗人ACAT-2抗体的免疫组化分析表明，ACAT-2定位于大鼠小肠绒毛-隐窝轴。抗ACAT-2抗体可显著降低糖尿病大鼠肠道ACAT活性，但抗ACAT-1抗体则无此作用。最后，在糖尿病大鼠肠道ACAT-2的蛋白和mRNA水平显着增加相比，在control rates. Conclusions，我们的数据表明，ACAT-2同工酶是负责增加肠道ACAT活性的糖尿病大鼠，这表明ACAT-2在糖尿病患者血脂异常的重要作用。
Objective-Diabetes-induced dyslipidemia is seen in streptozotocin-induced diabetic rats. This is caused, in part, by elevated intestinal acyl-coenzyme A: cholesterol acyltransferase (ACAT) activity. Because two ACAT isozymes (ACAT-1 and ACAT-2) were identified, in the present study we determined which ACAT isozyme was involved in the elevated intestinal ACAT activity in diabetic rats.Methods and Results-We cloned a full-length cDNA of rat ACAT-2. Its overexpression in ACAT-deficient AC29 cells demonstrated that the ACAT activity is derived from the cloned cDNA, and a 45-kDa protein of rat ACAT-2 cross-reacts with an anti-human ACAT-2 antibody. The tissue distribution of rat ACAT-2 mRNA revealed its restricted expression to liver and small intestine. Immunohistochemical analyses using an anti-human ACAT-2 antibody demonstrated that ACAT-2 is localized in villus-crypt axis of rat small intestine. The intestinal ACAT activity in diabetic rats was significantly immunodepleted by an anti-ACAT-2 antibody but not by an anti-ACAT-1 antibody. Finally, intestinal ACAT-2 in diabetic rats significantly increased at both protein and mRNA levels as compared with that in control rats.Conclusions-Our data demonstrate that ACAT-2 isozyme is responsible for the increased intestinal ACAT activity of diabetic rats, suggesting an important role of ACAT-2 for dyslipidemia in diabetic patients.