Parasites, Hosts and Diseases

"autophagy"

Original Articles

4-Hydroxybenzaldehyde Restricts the Intracellular Growth of Toxoplasma gondii by Inducing SIRT1-Mediated Autophagy in Macrophages: Jina lee, Jae-Won Choi, Hye Young Han, Woo Sik Kim, Ha-Yeon Song, Eui-Baek Byun, Eui-Hong Byun, Young-Ha Lee, Jae-Min Yuk; Korean J Parasitol 2020;58(1):7-14.
Published online February 29, 2020; DOI: https://doi.org/10.3347/kjp.2020.58.1.7

Abstract
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Toxoplasma gondii is an intracellular protozoan parasite that infects approximately one third of the human popu- lation worldwide. Considering the toxicity and side effects of anti-toxoplasma medications, it is important to develop effec- tive 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 expres- sion 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.

Citations

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Nature Communications.2025;[Epub] CrossRef
Neospora caninum infection specifically suppresses the expression of a host lncRNA XR_001919077.1 to facilitate parasite propagation by modulating host cell mitochondrial function and autophagy
Shan-Shan Zhao, De-Liang Tao, Jin-Ming Chen, Ming-Yi Zhang, Xin Yang, Jun-Ke Song, Qun Liu, Guang-Hui Zhao, Björn F. C. Kafsack
Microbiology Spectrum.2025;[Epub] CrossRef
Synthesis, structural characterization, in silico ADMET and molecular docking studies of a Schiff base derived from 4-hydroxybenzaldehyde and 4-aminobenzoic acid
Patryk Nowak, Artur Sikorski
New Journal of Chemistry.2025; 49(14): 5940. CrossRef
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Carme Casadevall, Bella Agranovich, Cesar Jesse Enríquez-Rodríguez, Rosa Faner, Sergi Pascual-Guàrdia, Ady Castro-Acosta, Ramon Camps-Ubach, Judith Garcia-Aymerich, Esther Barreiro, Eduard Monsó, Luis Seijo, Juan José Soler-Cataluña, Salud Santos, Germán
International Journal of Molecular Sciences.2025; 26(10): 4526. CrossRef
The role of host autophagy in intracellular protozoan parasites diseases
Rafael Cardoso Maciel Costa Silva, Jhones Sousa Ribeiro, Thalita Santos de Moraes de Farias, Leonardo Holanda Travassos
Archives of Biochemistry and Biophysics.2024; 761: 110186. CrossRef
Structural diversity of cocrystals formed from acridine and two isomers of hydroxybenzaldehyde: 3-hydroxybenzaldehyde and 4-hydroxybenzaldehyde
Patryk Nowak, Artur Sikorski
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Protective effect of benzaldehyde combined with albendazole against brain injury induced by Angiostrongylus cantonensis infection in mice
Kuang-Yao Chen, Chien-Ju Cheng, Yi-Ju Chen, Cheng-Hsun Chiu, Lian-Chen Wang
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Kuang-Yao Chen, Yi-Ju Chen, Chien-Ju Cheng, Kai-Yuan Jhan, Lian-Chen Wang
Biomolecules.2022; 12(2): 177. CrossRef
Neospora caninum infection induced mitochondrial dysfunction in caprine endometrial epithelial cells via downregulating SIRT1
De-Liang Tao, Shan-Shan Zhao, Jin-Ming Chen, Xi Chen, Xin Yang, Jun-Ke Song, Qun Liu, Guang-Hui Zhao
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Ao Cheng, Huanan Zhang, Baike Chen, Shengyao Zheng, Hongyi Wang, Yijia Shi, Siyao You, Ming Li, Liping Jiang
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SIRT1 Promotes Host Protective Immunity against Toxoplasma gondii by Controlling the FoxO-Autophagy Axis via the AMPK and PI3K/AKT Signalling Pathways
Jina Lee, Jinju Kim, Jae-Hyung Lee, Yong Min Choi, Hyeonil Choi, Hwan-Doo Cho, Guang-Ho Cha, Young-Ha Lee, Eun-Kyeong Jo, Byung-Hyun Park, Jae-Min Yuk
International Journal of Molecular Sciences.2022; 23(21): 13578. CrossRef
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Kai Dong, Ziyang Jiang, Jianhui Zhang, Hanxiao Qin, Jianping Chen, Qiwei Chen
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Urolithin-A attenuates neurotoxoplasmosis and alters innate response towards predator odor
Sijie Tan, Wen Han Tong, Ajai Vyas
Brain, Behavior, & Immunity - Health.2020; 8: 100128. CrossRef
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Minmin Wu, Obed Cudjoe, Jilong Shen, Ying Chen, Jian Du
Frontiers in Microbiology.2020;[Epub] CrossRef

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Identification of Atg8 Isoform in Encysting Acanthamoeba: Eun-Kyung Moon, Yeonchul Hong, Dong-Il Chung, Hyun-Hee Kong; Korean J Parasitol 2013;51(5):497-502.
Published online October 31, 2013; DOI: https://doi.org/10.3347/kjp.2013.51.5.497

Abstract
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Autophagy-related protein 8 (Atg8) is an essential component of autophagy formation and encystment of cyst-forming parasites, and some protozoa, such as, Acanthamoeba, Entamoeba, and Dictyostelium, have been reported to possess a type of Atg8. In this study, an isoform of Atg8 was identified and characterized in Acanthamoeba castellanii (AcAtg8b). AcAtg8b protein was found to encode 132 amino acids and to be longer than AcAtg8 protein, which encoded 117 amino acids. Real-time PCR analysis showed high expression levels of AcAtg8b and AcAtg8 during encystation. Fluorescence microscopy demonstrated that AcAtg8b is involved in the formation of the autophagosomal membrane. Chemically synthesized siRNA against AcAtg8b reduced the encystation efficiency of Acanthamoeba, confirming that AcAtg8b, like AcAtg8, is an essential component of cyst formation in Acanthamoeba. Our findings suggest that Acanthamoeba has doubled the number of Atg8 gene copies to ensure the successful encystation for survival when 1 copy is lost. These 2 types of Atg8 identified in Acanthamoeba provide important information regarding autophagy formation, encystation mechanism, and survival of primitive, cyst-forming protozoan parasites.

Citations

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Proliferation of Toxoplasma gondii Suppresses Host Cell Autophagy: Youn-Jin Lee, Hyun-Ouk Song, Young-Ha Lee, Jae-Sook Ryu, Myoung-Hee Ahn; Korean J Parasitol 2013;51(3):279-287.
Published online June 30, 2013; DOI: https://doi.org/10.3347/kjp.2013.51.3.279

Abstract
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Autophagy is a process of cytoplasmic degradation of endogenous proteins and organelles. Although its primary role is protective, it can also contribute to cell death. Recently, autophagy was found to play a role in the activation of host defense against intracellular pathogens. The aims of our study was to investigate whether host cell autophagy influences Toxoplasma gondii proliferation and whether autophagy inhibitors modulate cell survival. HeLa cells were infected with T. gondii with and without rapamycin treatment to induce autophagy. Lactate dehydrogenase assays showed that cell death was extensive at 36-48 hr after infection in cells treated with T. gondii with or without rapamycin. The autophagic markers, LC3 II and Beclin 1, were strongly expressed at 18-24 hr after exposure as shown by Western blotting and RT-PCR. However, the subsequent T. gondii proliferation suppressed autophagy at 36 hr post-infection. Pre-treatment with the autophagy inhibitor, 3-methyladenine (3-MA), down-regulated LC3 II and Beclin 1. The latter was also down-regulated by calpeptin, a calpain inhibitor. Monodansyl cadaverine (MDC) staining detected numerous autophagic vacuoles (AVs) at 18 hr post-infection. Ultrastructural observations showed T. gondii proliferation in parasitophorous vacuoles (PVs) coinciding with a decline in the numbers of AVs by 18 hr. FACS analysis failed to confirm the presence of cell apoptosis after exposure to T. gondii and rapamycin. We concluded that T. gondii proliferation may inhibit host cell autophagy and has an impact on cell survival.

Citations

Citations to this article as recorded by

Modulation of autophagy as a therapeutic strategy for Toxoplasma gondii infection
Ao Cheng, Huanan Zhang, Baike Chen, Shengyao Zheng, Hongyi Wang, Yijia Shi, Siyao You, Ming Li, Liping Jiang
Frontiers in Cellular and Infection Microbiology.2022;[Epub] CrossRef
Myrislignan Induces Redox Imbalance and Activates Autophagy in Toxoplasma gondii
Jili Zhang, Jia Chen, Kun Lv, Bing Li, Biqing Yan, Lei Gai, Chaolu Shi, Xinnian Wang, Hongfei Si, Jiyu Zhang
Frontiers in Cellular and Infection Microbiology.2021;[Epub] CrossRef
4-Hydroxybenzaldehyde Restricts the Intracellular Growth of Toxoplasma gondii by Inducing SIRT1-Mediated Autophagy in Macrophages
Jina lee, Jae-Won Choi, Hye Young Han, Woo Sik Kim, Ha-Yeon Song, Eui-Baek Byun, Eui-Hong Byun, Young-Ha Lee, Jae-Min Yuk
The Korean Journal of Parasitology.2020; 58(1): 7. CrossRef
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