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

The journal of physiological sciences

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