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Toxoplasma gondii protects against H 2 O 2 ‐induced apoptosis in ARPE‐19 cells through the transcriptional regulation of apoptotic elements and downregulation of the p38 MAPK pathway
Author(s) -
Choi SiHwan,
Park Sung Jun,
Cha GuangHo,
Quan Juan Hua,
Chang NamSik,
Ahn MyoungHee,
Shin DaeWhan,
Lee YoungHa
Publication year - 2011
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2011.02113.x
Subject(s) - toxoplasma gondii , p38 mitogen activated protein kinases , apoptosis , biology , mapk/erk pathway , microbiology and biotechnology , western blot , reactive oxygen species , kinase , dna fragmentation , programmed cell death , multiplicity of infection , viability assay , cell , immunology , antibody , biochemistry , gene
. Purpose: Toxoplasmosis, which is caused by the protozoan parasite Toxoplasma gondii , can lead to severe visual impairment. T. gondii inhibits or delays programmed cell death caused by various apoptotic triggers; however, the mechanisms involved in the T . gondii ‐induced suppression of apoptosis in retinal cells have not been analysed in detail. Methods: We investigated the role of T . gondii infection in H 2 O 2 ‐induced apoptosis in human retinal pigment epithelial cells (ARPE‐19) by monitoring the activities of apoptosis‐regulating molecules and mitogen‐activated protein kinases (MAPKs), including p38 MAPK. We also examined the gene downstream from p38 MAPK. Results: T. gondii infection significantly inhibited the cellular toxicity of H 2 O 2 (500 μ m ) and increased cell viability in a multiplicity of infection (MOI)‐dependent manner by reducing DNA fragmentation and reactive oxygen species (ROS) generation in ARPE‐19 cells. Western blot analysis also showed that T . gondii infection prevented the host cell expression of pro‐apoptotic factors, such as Bad and Bax, and the activation of caspase‐3. Infection with T . gondii increased the expression of the anti‐apoptotic factor Bcl‐2 in ARPE‐19 cells under oxidative stress. In accordance with these findings, Toxoplasma infection was protective enough to suppress the phosphorylation of p38 MAPK following H 2 O 2 treatment. Exposure to H 2 O 2 increased the expression of heme oxygenase‐1 (HO‐1) in ARPE‐19 cells, and its expression was significantly inhibited in H 2 O 2 ‐treated infected cells. Conclusion: The protective function of T . gondii infection against ROS‐induced apoptosis results from changes in the expression of apoptotic molecules and the downregulation of stress‐induced intracellular signalling.