The journal of physiological sciences | |
4-Hydroxybenzaldehyde Restricts the Intracellular Growth of Toxoplasma gondii by Inducing SIRT1-Mediated Autophagy in Macrophages | |
article | |
Jina Lee1  Jae-Won Choi1  Hye Young Han1  Woo Sik Kim2  Ha-Yeon Song2  Eui-Baek Byun2  Eui-Hong Byun3  Young-Ha Lee1  Jae-Min Yuk1  | |
[1] Department of Infection Biology and Medical Science, College of Medicine, Chungnam National University;Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute;Department of Food Science and Technology, Kongju National University | |
关键词: Toxoplasma gondii; toxoplasmosis; autophagy; sirtinol; 4-hydroxybenzaldehyde; NAD-dependent protein deacetylase sirtuin-1; LC3-phosphatidylethanolamine conjugate; | |
DOI : 10.3347/kjp.2020.58.1.7 | |
来源: Springer | |
【 摘 要 】
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.
【 授权许可】
Unknown
【 预 览 】
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