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http://dx.doi.org/10.3347/kjp.2020.58.1.7

4-Hydroxybenzaldehyde Restricts the Intracellular Growth of Toxoplasma gondii by Inducing SIRT1-Mediated Autophagy in Macrophages  

Lee, Jina (Department of Infection Biology and Medical Science, College of Medicine, Chungnam National University)
Choi, Jae-Won (Department of Infection Biology and Medical Science, College of Medicine, Chungnam National University)
Han, Hye Young (Department of Infection Biology and Medical Science, College of Medicine, Chungnam National University)
Kim, Woo Sik (Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute)
Song, Ha-Yeon (Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute)
Byun, Eui-Baek (Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute)
Byun, Eui-Hong (Department of Food Science and Technology, Kongju National University)
Lee, Young-Ha (Department of Infection Biology and Medical Science, College of Medicine, Chungnam National University)
Yuk, Jae-Min (Department of Infection Biology and Medical Science, College of Medicine, Chungnam National University)
Publication Information
Parasites, Hosts and Diseases / v.58, no.1, 2020 , pp. 7-14 More about this Journal
Abstract
Toxoplasma gondii is an intracellular protozoan parasite that infects approximately one third of the human population worldwide. Considering the toxicity and side effects of anti-toxoplasma medications, it is important to develop effective drug alternatives with fewer and less severe off-target effects. In this study, we found that 4-hydroxybenzaldehyde (4-HBA) induced autophagy and the expression of NAD-dependent protein deacetylase sirtuin-1 (SIRT1) in primary murine bone marrow-derived macrophages (BMDMs). Interestingly, treatment of BMDMs with 4-HBA significantly reduced the number of macrophages infected with T. gondii and the proliferation of T. gondii in infected cells. This effect was impaired by pretreating the macrophages with 3-methyladenine or wortmannin (selective autophagy inhibitors) or with sirtinol or EX527 (SIRT1 inhibitors). Moreover, we found that pharmacological inhibition of SIRT1 prevented 4-HBA-mediated expression of LC3-phosphatidylethanolamine conjugate (LC3-II) and the colocalization of T. gondii parasitophorous vacuoles with autophagosomes in BMDMs. These data suggest that 4-HBA promotes antiparasitic host responses by activating SIRT1-mediated autophagy, and 4-HBA might be a promising therapeutic alternative for the treatment of toxoplasmosis.
Keywords
Toxoplasma gondii; toxoplasmosis; autophagy; sirtinol; 4-hydroxybenzaldehyde; NAD-dependent protein deacetylase sirtuin-1; LC3-phosphatidylethanolamine conjugate;
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