title: Negative regulation of ERK1/2 by PI3K is required for the protective effects of Pyropia yezoensis peptide against perfluorooctane sulfonate-induced endoplasmic reticulum stress.
abstract: Perfluorooctane sulfonate (PFOS) is a stable fluorosurfactant, which causes adverse effects in various organisms. The present study was designed to investigate the effects of Pyropia yezoensis peptide (PYP), a peptide comprised of 11 residues (ALEGGKSSGGG), on PFOS-induced endoplasmic reticulum (ER) stress in Chang cells. PFOS exposure (400 µM) for 24 h significantly decreased cell viability, which was upregulated by 250‑1,000 pg/ml PYP treatment. Exposure to PFOS also significantly increased expression of the ER stress response protein, glucose-regulated protein 78 (GRP78), and phosphorylation of extracellular signal‑regulated kinase 1/2 (ERK1/2). These elevations were significantly decreased by PYP (250 pg/ml), and, in particular, the PFOS‑induced GRP78 upregulation was decreased following treatment with 10 µM SL327, an ERK‑kinase inhibitor. However, PYP‑induced decreases in GRP78 expression and ERK1/2 phosphorylation were upregulated following treatment with LY294002 (20 µM), a phosphatidylinositol‑3 kinase (PI3K) inhibitor. PFOS-induced apoptosis was also significantly attenuated by PYP (250 pg/ml) treatment, and the PYP‑induced reduction in apoptosis was abolished by inhibition of PI3K. These findings indicate that negative regulation of ERK1/2 by PI3K is essential for the protective effects of PYP against PFOS-induced cell death, suggesting that PYP may be a candidate for therapeutic use.
authors.affiliation: Cell Biology Laboratory, Institute of Fisheries Sciences, Pukyong National University, Busan 46041, Republic of Korea.
authors.forename: Jeong Hwan
authors.initials: JH
authors.lastname: Oh
authors.affiliation: Cell Biology Laboratory, Institute of Fisheries Sciences, Pukyong National University, Busan 46041, Republic of Korea.
authors.forename: Eun-Young
authors.initials: EY
authors.lastname: Kim
authors.affiliation: Department of Marine Bio‑Materials and Aquaculture, Pukyong National University, Busan 48513, Republic of Korea.
authors.forename: Youn Hee
authors.initials: YH
authors.lastname: Choi
authors.affiliation: Cell Biology Laboratory, Institute of Fisheries Sciences, Pukyong National University, Busan 46041, Republic of Korea.
authors.forename: Taek-Jeong
authors.initials: TJ
authors.lastname: Nam
mesh_terms: D017738:Alkanesulfonic Acids / Q000633:toxicity; D000595:Amino Acid Sequence; D000607:Aminoacetonitrile / Q000031:analogs & derivatives / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D005466:Fluorocarbons / Q000633:toxicity; D006360:Heat-Shock Proteins; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009025:Morpholines / Q000494:pharmacology; D010455:Peptides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D020011:Protective Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D000461:Rhodophyta / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D017738:Alkanesulfonic Acids; D000607:Aminoacetonitrile; D002867:Chromones; D000091342:Endoplasmic Reticulum Chaperone BiP; D005466:Fluorocarbons; D006360:Heat-Shock Proteins; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D009025:Morpholines; D010455:Peptides; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D020011:Protective Agents; D043562:Receptors, G-Protein-Coupled; C000717247:HSPA5 protein, human; C424127:SL 327; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C076994:perfluorooctane sulfonic acid