Suppressors for Human Epidermal Growth Factor Receptor 2/4 (HER2/4) : A New Family of Anti-Toxoplasmic Agents in ARPE-19 Cells :A New Family of Anti-Toxoplasmic Agents in ARPE-19 Cells

Yeong Hoon Kim; Lokraj Bhatt; Hye-Jin Ahn; Zhaoshou Yang; Won-Kyu Lee; Ho-Woo Nam

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자료유형: 학술저널

저자정보: Yeong Hoon Kim (The Catholic University of K) Lokraj Bhatt (The Catholic University of Korea) Hye-Jin Ahn (The Catholic University of Korea) Zhaoshou Yang (The Catholic University of Korea) Won-Kyu Lee (Osong Medical Innovation Foundation) Ho-Woo Nam (The Catholic University of Korea)

저널정보: 대한기생충학열대의학회 Parasites, Hosts and Diseases The Korean Journal of Parasitology Vol.55 No.5

발행연도: 2017.10

수록면: 491 - 503 (13page)

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The effects of tyrosine kinase inhibitors (TKIs) were evaluated on growth inhibition of intracellular Toxoplasma gondii in host ARPE-19 cells. The number of tachyzoites per parasitophorous vacuolar membrane (PVM) was counted after treatment with TKIs. T. gondii protein expression was assessed by western blot. Immunofluorescence assay was performed using Programmed Cell Death 4 (PDCD4) and T. gondii GRA3 antibodies. The TKIs were divided into 3 groups; non-epidermal growth factor receptor (non-EGFR), anti-human EGFR 2 (anti-HER2), and anti-HER2/4 TKIs, respectively. Group I TKIs (nintedanib, AZD9291, and sunitinib) were unable to inhibit proliferation without destroying host cells. Group II TKIs (lapatinib, gefitinib, erlotinib, and AG1478) inhibited proliferation up to 98% equivalent to control pyrimethamine (5μM) at 20 μM and higher, without affecting host cells. Group III TKIs (neratinib, dacomitinib, afatinib, and pelitinib) inhibited proliferation up to 98% equivalent to pyrimethamine at 1-5 μM, but host cells were destroyed at 10-20 μM. In Group I, TgHSP90 and SAG1 inhibitions were weak, and GRA3 expression was moderately inhibited. In Group II, TgHSP90 and SAG1 expressions seemed to be slightly enhanced, while GRA3 showed none to mild inhibition; however, AG1478 inhibited all proteins moderately. Protein expression was blocked in Group III, comparable to pyrimethamine. PDCD4 and GRA3 were well localized inside the nuclei in Group I, mildly disrupted in Group II, and were completely disrupted in Group III. This study suggests the possibility of a vital T. gondii TK having potential HER2/4 properties, thus anti-HER2/4 TKIs may inhibit intracellular parasite proliferation with minimal adverse effects on host cells.

#Toxoplasma gondii #intracellular #growth #inhibition #TKIs #HER2 #HER2/4 #ARPE-19

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