Korean J Parasitol.  2020 Jun;58(3):249-255. 10.3347/kjp.2020.58.3.249.

Secretome Analysis of Host Cells Infected with Toxoplasma gondii after Treatment of Human Epidermal Growth Factor Receptor 2/4 Inhibitors

• Kim HJ
• Ahn HJ
• Kang H
• Park J
• Oh Sg
• Choi S
• Lee WK
• Nam HW

• KMID: 2505092
• DOI: http://doi.org/10.3347/kjp.2020.58.3.249

Abstract

Toxoplasma gondii, a ubiquitous, intracellular parasite of the phylum Apicomplexa, infects an estimated one-third of the human population as well as a broad range of warm-blooded animals. We have observed that some tyrosine kinase inhibitors suppressed the growth of T. gondii within host ARPE-10 cells. Among them, afatinib, human epithermal growth factor receptor 2 and 4 (HER2/4) inhibitor, may be used as a therapeutic agent for inhibiting parasite growth with minimal adverse effects on host. In this report, we conducted a proteomic analysis to observe changes in host proteins that were altered via infection with T. gondii and the treatment of HER2/4 inhibitors. Secreting proteins were subjected to a procedure of micor basic reverse phase liquid chromatography, nano-liquid chromatography-mass spectrometry, and ingenuity pathway analysis serially. As a result, the expression level of heterogeneous nuclear ribonucleoprotein K, semaphorin 7A, a GPI membrane anchor, serine/threonine-protein phosphatase 2A, and calpain small subunit 1 proteins were significantly changed, and which were confirmed further by western blot analysis. Changes in various proteins, including these 4 proteins, can be used as a basis for explaining the effects of T. gondii infections and HER2/4 inhibitors.

Keyword

HER2/4 inhibitors; secretome; semaphorin 7A; calpain small subunit 1