title: The proliferative effects of Pyropia yezoensis peptide on IEC-6 cells are mediated through the epidermal growth factor receptor signaling pathway.
abstract: For a number of years, seaweed has been used as a functional food in Asian countries, particularly in Korea, Japan and China. Pyropia yezoensis is a marine red alga that has potentially beneficial biological activities. In this study, we examined the mechanisms through which a Pyropia yezoensis peptide [PYP1 (1-20)] induces the proliferation of IEC-6 cells, a rat intestinal epithelial cell line, and the involvement of the epidermal growth factor receptor (EGFR) signaling pathway. First, cell viability assay revealed that PYP1 (1-20) induced cell proliferation in a concentration-dependent manner. Subsequently, we examined the mechanisms responsible for this induction of proliferation induced by PYP1 (1-20). EGFR is widely expressed in mammalian epithelial tissues, and the binding of this ligand affects a variety of cell physiological parameters, such as cell growth and proliferation. PYP1 (1-20) increased the expression of EGFR, Shc, growth factor receptor-bound protein 2 (Grb2) and son of sevenless (SOS). EGFR also induced the activation of the Ras signaling pathway through Raf, MEK and extracellular signal-regulated kinase (ERK) phosphorylation. In addition, cell cycle analysis revealed the expression of cell cycle-related proteins. The results demonstrated an increased number of cells in the G1 phase and an enhanced cell proliferation. In addition, the upregulation of cyclin D, cyclin E, Cdk2, Cdk4 and Cdk6 was observed accompanied by a decreased in p21 and p27 expression. These findings suggest that PYP1 (1-20) stimulates the proliferation of rat IEC-6 cells by activating the EGFR signaling pathway. Therefore, PYP1 (1-20) may be a potential source for the development of bio-functional foods which promotes the proliferation of intestinal epithelial cells.
authors.affiliation: Department of Food Science and Nutrition, Pukyong National University, Busan 608-737, Republic of Korea.
authors.forename: Min-Kyeong
authors.initials: MK
authors.lastname: Lee
authors.affiliation: Institute of Fisheries Science, Pukyong National University, Busan 619-911, Republic of Korea.
authors.forename: In-Hye
authors.initials: IH
authors.lastname: Kim
authors.affiliation: Institute of Fisheries Science, Pukyong National University, Busan 619-911, Republic of Korea.
authors.forename: Youn-Hee
authors.initials: YH
authors.lastname: Choi
authors.affiliation: Department of Food Science and Nutrition, Pukyong National University, Busan 608-737, Republic of Korea.
authors.forename: Jeong-Wook
authors.initials: JW
authors.lastname: Choi
authors.affiliation: Institute of Fisheries Science, Pukyong National University, Busan 619-911, Republic of Korea.
authors.forename: Young-Min
authors.initials: YM
authors.lastname: Kim
authors.affiliation: Department of Food Science and Nutrition, Pukyong National University, Busan 608-737, Republic of Korea.
authors.forename: Taek-Jeong
authors.initials: TJ
authors.lastname: Nam
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism*; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors; D005786:Gene Expression Regulation / Q000187:drug effects; D007413:Intestinal Mucosa; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism; D051381:Rats; D000461:Rhodophyta / Q000737:chemistry*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D018797:Cell Cycle Proteins; D010455:Peptides; D047428:Protein Kinase Inhibitors; D066246:ErbB Receptors; D048049:Extracellular Signal-Regulated MAP Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D016283:Proto-Oncogene Proteins p21(ras)