Toxoplasma gondii protects against H₂O₂‐induced apoptosis in ARPE‐19 cells through the transcriptional regulation of apoptotic elements and downregulation of the p38 MAPK pathway

Abstract

ABSTRACT.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 lm) 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 proapoptotic 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 stressinduced intracellular signalling.

Differential effects of bevacizumab, ranibizumab and aflibercept on cell viability, phagocytosis and mitochondrial bioenergetics of retinal pigment epithelial cell

“…Activation of the MAPK family is redox sensitive (Choi et al. ), and the MAPK signalling is involved in acrolein‐induced cell toxicity (Tanel & Averill‐Bates ; Moretto et al. ).…”

Disruption of outer blood-retinal barrier by Toxoplasma gondii-infected monocytes is mediated by paracrinely activated FAK signaling

“…Therefore, pathogenesis of lesions at outer BRB was investigated by using T . gondii -infected cells instead of tachyzoites that were commonly used in other studies to directly infect RPE [10–12]. …”

Inflammatory Cytokines Protect Retinal Pigment Epithelial Cells from Oxidative Stress-Induced Death

“…Other studies have also shown that H 2 O 2 , another oxidative agent, induces RPE cell death characterized by the production of ROS [47]–[49], cytochrome c release [50], [51], DNA fragmentation [49], [51], Annexin V-binding [52], TUNEL-staining [50], and caspase-3 activation [47], [49], [51], [53]. RPE cells can be protected from H 2 O 2 -induced cell death by treatment with antioxidants such as ascorbate (vitamin C) [54], N-acetylcysteine [47], and quercetin [55].…”