KMID : 0942820060050020096
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Journal of Korean Brain Tumor Society 2006 Volume.5 No. 2 p.96 ~ p.102
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Activation of Mitogen-Activated Protein Kinase Pathway in Glioma Cells Infected with Toxoplasma gondii
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Park Byung-Hyun
Lee Hyun-Sung Lee Jong-Soo Yang Seong-Hwan Shin Dae-Whan Lee Young-Ha
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Abstract
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Objective: Gliomas are the most common primary brain tumors in adults. Toxoplasma gondii is an obligate intracellular parasite with a high affinity for brain cells. Mitogen-activated protein kinases(MAPKs) are known to regulate the host cell invasion, although little is known regarding MAPK signaling in Toxoplasma-infected glioma cells.
Methods: U87MG and U373MG cells were infected with tachyzoites of the RH strain of T. gondii, and the kinetics of MAPK activation were determined by immunoblotting. We also determined the effects of MAPK inhibitors on glioma cell growth and T. gondii replication using the 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetraterazolium bromide(MTT£» Sigma) method and [3H]-uracil incorporation assays.
Results: There were no significant differences in the levels of unphosphorylated MAPK at different incubation times in the Toxoplasma-infected U373MG cells. T. gondii induced the activation of extracellular signal-regulated kinase(ERK) 1/2, p30MAPK, and c-Jun N-terminal kinase(JNK)1/2 within 30 minutes of infection, and showed differential kinetics of activation for each MAPK. The activation of ERK1/2, p38MAPK, and JNK1/2 in Toxoplasma-infected glioma cells was blocked by PD98059, SB202190, and SB203580, respectively. T. gondii replication was inhibited in a dose-dependent manner by the addition of MAPK inhibitors to Toxoplasma-infected glioma cells.
Conclusion: Infection with T. gondii induces the activation of MAPKs in glioma cells, and this activation can be blocked by the addition of kinase-specific inhibitors. These results suggest that the MAPK pathway plays a role in the invasion of glioma cells with T. gondii.
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KEYWORD
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Glioma, Toxoplasma gondii, Mitogen-activated protein kinase(MAPK), MAPK inhibitor
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