PMID- 32145722
OWN - NLM
STAT- MEDLINE
DCOM- 20200806
LR  - 20200806
IS  - 1738-0006 (Electronic)
IS  - 0023-4001 (Print)
IS  - 0023-4001 (Linking)
VI  - 58
IP  - 1
DP  - 2020 Feb
TI  - 4-Hydroxybenzaldehyde Restricts the Intracellular Growth of Toxoplasma gondii by 
      Inducing SIRT1-Mediated Autophagy in Macrophages.
PG  - 7-14
LID - 10.3347/kjp.2020.58.1.7 [doi]
AB  - 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.
FAU - Lee, Jina
AU  - Lee J
AD  - Department of Infection Biology and Medical Science, College of Medicine, 
      Chungnam National University, Daejeon 35015, Korea.
AD  - Infection Control Convergence Research Center, College of Medicine, Chungnam 
      National University, Daejeon 35015, Korea.
FAU - Choi, Jae-Won
AU  - Choi JW
AD  - Department of Infection Biology and Medical Science, College of Medicine, 
      Chungnam National University, Daejeon 35015, Korea.
AD  - Infection Control Convergence Research Center, College of Medicine, Chungnam 
      National University, Daejeon 35015, Korea.
FAU - Han, Hye Young
AU  - Han HY
AD  - Department of Infection Biology and Medical Science, College of Medicine, 
      Chungnam National University, Daejeon 35015, Korea.
FAU - Kim, Woo Sik
AU  - Kim WS
AD  - Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, 
      Jeongeup 56212, Korea.
FAU - Song, Ha-Yeon
AU  - Song HY
AD  - Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, 
      Jeongeup 56212, Korea.
FAU - Byun, Eui-Baek
AU  - Byun EB
AD  - Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, 
      Jeongeup 56212, Korea.
FAU - Byun, Eui-Hong
AU  - Byun EH
AD  - Department of Food Science and Technology, Kongju National University, Yesan 
      32439, Korea.
FAU - Lee, Young-Ha
AU  - Lee YH
AD  - Department of Infection Biology and Medical Science, College of Medicine, 
      Chungnam National University, Daejeon 35015, Korea.
FAU - Yuk, Jae-Min
AU  - Yuk JM
AD  - Department of Infection Biology and Medical Science, College of Medicine, 
      Chungnam National University, Daejeon 35015, Korea.
AD  - Infection Control Convergence Research Center, College of Medicine, Chungnam 
      National University, Daejeon 35015, Korea.
LA  - eng
GR  - 2017R1A5A2015385,2019R1C1C1004431,2018M2A2B3A02072071/National Research 
      Foundation of Korea/
GR  - Ministry of Science, ICT and Future Planning/
PT  - Journal Article
DEP - 20200229
PL  - Korea (South)
TA  - Korean J Parasitol
JT  - The Korean journal of parasitology
JID - 9435800
RN  - 0 (Benzaldehydes)
RN  - EC 3.5.1.- (Sirtuin 1)
RN  - O1738X3Y38 (4-hydroxybenzaldehyde)
SB  - IM
MH  - Animals
MH  - *Autophagy
MH  - Benzaldehydes/*pharmacology
MH  - Cells, Cultured
MH  - Depression, Chemical
MH  - Macrophages/*physiology
MH  - Mice, Inbred C57BL
MH  - *Sirtuin 1
MH  - Toxoplasma/*growth & development
PMC - PMC7066436
OTO - NOTNLM
OT  - 4-hydroxybenzaldehyde
OT  - LC3-phosphatidylethanolamine conjugate
OT  - NAD-dependent protein deacetylase sirtuin-1
OT  - Toxoplasma gondii
OT  - autophagy
OT  - sirtinol
OT  - toxoplasmosis
COIS- The authors have no financial conflict of interests.
EDAT- 2020/03/09 06:00
MHDA- 2020/08/07 06:00
PMCR- 2020/02/01
CRDT- 2020/03/09 06:00
PHST- 2019/09/02 00:00 [received]
PHST- 2019/11/04 00:00 [accepted]
PHST- 2020/03/09 06:00 [entrez]
PHST- 2020/03/09 06:00 [pubmed]
PHST- 2020/08/07 06:00 [medline]
PHST- 2020/02/01 00:00 [pmc-release]
AID - kjp.2020.58.1.7 [pii]
AID - kjp-58-1-7 [pii]
AID - 10.3347/kjp.2020.58.1.7 [doi]
PST - ppublish
SO  - Korean J Parasitol. 2020 Feb;58(1):7-14. doi: 10.3347/kjp.2020.58.1.7. Epub 2020 
      Feb 29.