A novel regulatory pathway for cholesterol degradation via lactostatin.

Abstract

Our group previously discovered a novel hypocholesterolemic pentapeptide (IIAEK: Ile-Ile-Ala-Glu-Lys, or what we describe as "lactostatin") derived from bovine milk beta-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 7alpha-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.

• Authors: Kensei Morikawa, Itsuo Kondo, Yoshihiro Kanamaru, Satoshi Nagaoka
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 352 Issue 3 Pg. 697-702 (Jan 19 2007) ISSN: 0006-291X [Print] United States
• PMID: 17141196 (Publication Type: Journal Article)

Chemical References

• Calcium Channels
• Oligopeptides
• lactostatin
• Cholesterol
• Mitogen-Activated Protein Kinases

Topics

• Calcium Channels (metabolism)
• Cell Line
• Cholesterol (metabolism)
• Dose-Response Relationship, Drug
• Gene Expression Regulation (drug effects, physiology)
• Hepatocytes (drug effects, metabolism)
• Humans
• Mitogen-Activated Protein Kinases (metabolism)
• Oligopeptides (administration & dosage)
• Signal Transduction (drug effects, physiology)