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.