Parasites, Hosts and Diseases

  • 제58권1호
  • /
  • Pages.7-14
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  • 2020
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  • 2982-5164(pISSN)
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  • 1738-0006(eISSN)
대한기생충학·열대의학회 (The Korea Society for Parasitology and Tropical Medicine)
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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)
  • 투고 : 2019.09.02
  • 심사 : 2019.11.04
  • 발행 : 2020.02.29
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초록

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.

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