Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 352, Issue 3, Pages 697-702Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2006.11.090
Keywords
cholesterol; lactostatin; peptide; bile acid; HepG2; calcium channel; cholesterol 7 alpha-hydroxylase
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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.
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