A novel regulatory pathway for cholesterol degradation via lactostatin
A novel regulatory pathway for cholesterol degradation via lactostatin
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DOI：
10.1016/j.bbrc.2006.11.090
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发表时间：
2007-01-19
影响因子：
3.1
通讯作者：
Nagaoka, Satoshi
中科院分区：
文献类型：
--
作者：
Morikawa, Kensel;Kondo, Itsuo;Nagaoka, Satoshi
我们的研究小组以前发现了一种新的低胆固醇血症五肽（IIAEK：Ile-Ile-Ala-Glu-Lys，或我们称之为“乳糖抑制素”），来源于牛乳P-乳球蛋白。为了阐明Lactostatin降胆固醇作用的机制，我们在人肝细胞系HepG 2中筛选了Lactostatin诱导的靶基因和信号转导途径。出乎意料的是，我们发现水溶性乳糖抑制素可以激活胆固醇7 α-羟化酶（CYP 7A 1）基因的表达。丝裂原活化蛋白激酶（MAPK）抑制剂或钙（Ca 2+）通道阻滞剂的治疗阻断了这种激活。我们还发现，lactostatin调节细胞外信号调节激酶（ERK）的磷酸化和细胞内Ca 2+浓度。在这里，我们显示了一个新的监管途径参与钙通道相关的MAPK信号通路的乳糖抑制素介导的胆固醇降解。寡肽作为一种新的分子，在开发预防和改善高胆固醇血症和动脉粥样硬化的药物和功能性食品方面具有广阔的应用前景。(c)2006爱思唯尔公司All rights reserved.
Our group previously discovered a novel hypocholesterolemic pentapeptide (IIAEK: Ile-Ile-Ala-Glu-Lys, or what we describe as "lactostatin") derived from bovine milk P-lactoglobulin. To clarify the mechanism of the hypocholesterolemic action of lactostatin, we screened the target gene and signal transducing pathway induced by lactostatin in HepG2, a human liver cell line. Unexpectedly, we found that water-soluble lactostatin can activate cholesterol 7 alpha-hydroxylase (CYP7A1) gene expression. Treatment with mitogen-activated protein kinase (MAPK) inhibitor or calcium (Ca2+) channel blocker blocked this activation. We also found that lactostatin regulates the phosphorylation of extracellular signal-regulated kinase (ERK) and intracellular Ca2+ concentration. Here, we show the involvement of a new regulatory pathway in the calcium-channel-related MAPK signaling pathway of lactostatin-mediated cholesterol degradation. Oligopeptide shows promise as a new molecule for the development of medicines and functional foods to prevent and improve hypercholesterolemia and atherosclerosis. (c) 2006 Elsevier Inc. All rights reserved.