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Cytoprotective Role of Mitogen‐activated Protein Kinase Phosphatase‐1 in Light‐damaged Human Retinal Pigment Epithelial Cells
Author(s) -
LornejadSchäfer Mohammad Reza,
Schäfer Christine,
Schöffl Harald,
Frank Jürgen
Publication year - 2009
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1111/j.1751-1097.2008.00479.x
Subject(s) - ask1 , microbiology and biotechnology , kinase , programmed cell death , protein kinase a , p38 mitogen activated protein kinases , mitogen activated protein kinase , c jun , mitogen activated protein kinase kinase , map2k7 , biology , map kinase kinase kinase , cyclin dependent kinase 2 , apoptosis , chemistry , biochemistry , gene , transcription factor
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 (≥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.