title: Cytoprotective role of mitogen-activated protein kinase phosphatase-1 in light-damaged human retinal pigment epithelial cells.
abstract: The role of the mitogen-activated protein (MAP) kinase phosphatases (MKPs) in light-damaged cells is unclear. Therefore we investigated the involvement of MKP-1 in the regulation of apoptosis and cell survival mediated by MAP kinase pathways in light-damaged human retinal pigment epithelial cells (ARPE-19). Light dose-dependent changes in the expression of MKP-1 and in the phosphorylation status of the MAP kinases, c-Jun-N-terminal kinase (JNK) and p38 were demonstrated. Low light doses up to 2 J cm(-2) led to an upregulation of MKP-1 which resulted in the prevention of cell death by inactivating JNK kinase. However, higher light doses (> or =3 J cm(-2)) significantly reduced MKP-1 protein expression and subsequently led to an increased JNK kinase activity followed by a significant increase in cell death. JNK kinase inactivation by the JNK inhibitor SP600125 significantly reduced light-induced cell death, suggesting that the cytoprotective properties of MKP-1 are mediated mainly by the JNK MAP kinase pathway. Physiological concentrations of ascorbic acid or taurine were seen to prevent apoptosis and cell death in light-damaged ARPE-19 cells by reducing oxidative stress within cells, thus maintaining MKP-1 at high levels, leading to an inactivation of the JNK kinase pathway which resulted in an increased cell viability.
authors.affiliation: zet-Centre for Alternative and Complementary Methods to Animal Testing, Linz, Austria.
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Lornejad-Schäfer
authors.forename: Christine
authors.initials: C
authors.lastname: Schäfer
authors.forename: Harald
authors.initials: H
authors.lastname: Schöffl
authors.forename: Jürgen
authors.initials: J
authors.lastname: Frank
mesh_terms: D006801:Humans; D054639:Mitogen-Activated Protein Kinase Phosphatases / Q000378:metabolism*; D055213:Retinal Pigment Epithelium / Q000166:cytology / Q000201:enzymology* / Q000528:radiation effects
chemical_list: D054639:Mitogen-Activated Protein Kinase Phosphatases