PMID- 36557995
OWN - NLM
STAT- MEDLINE
DCOM- 20221226
LR  - 20221226
IS  - 1420-3049 (Electronic)
IS  - 1420-3049 (Linking)
VI  - 27
IP  - 24
DP  - 2022 Dec 13
TI  - PINK1/Parkin-Mediated Mitophagy Partially Protects against Inorganic 
      Arsenic-Induced Hepatic Macrophage Polarization in Acute Arsenic-Exposed Mice.
LID - 10.3390/molecules27248862 [doi]
LID - 8862
AB  - Inorganic arsenic is a well-known environmental toxicant and carcinogen, and 
      there is overwhelming evidence for an association between this metalloid 
      poisoning and hepatic diseases. However, the biological mechanism involved is not 
      well characterized. In the present study, we probed how inorganic arsenic 
      modulates the hepatic polarization of macrophages, as well as roles of 
      PTEN-induced kinase 1 (PINK1)/Parkin-mediated mitophagy participates in 
      regulating the metalloid-mediated macrophage polarization. Our results indicate 
      that acute arsenic exposure induced macrophage polarization with up-regulated 
      gene expression of inducible nitric oxide synthase (Inos) and arginase-1 (Arg1), 
      monocyte chemotactic protein-1 (Mcp-1) and macrophage inflammatory protein-2 
      (Mip-2), tumor necrosis factor (Tnf)-alpha, interleukin (Il)-1beta and Il-6, as well as 
      anti-inflammatory factors Il-4 and Il-10. In parallel, we demonstrated the 
      disrupted hepatic redox balance typically characterized by the up-regulation of 
      hydrogen peroxide (H(2)O(2)) and glutathione (GSH), and activation of 
      PINK1/Parkin-mediated mitophagy in the livers of acute arsenic-exposed mice. In 
      addition, our results demonstrate that it might be the PINK1/Parkin-mediated 
      mitophagy that renders hepatic macrophage refractory to arsenic-induced 
      up-regulation of the genes Inos, Mcp-1, Mip-2, Tnf-alpha, Il-1beta, Il-6 and Il-4. In 
      this regard, this is the first time the protective effects of 
      PINK1/Parkin-mediated mitophagy in inorganic arsenic-induced hepatic macrophage 
      polarization in vivo have been reported. These findings add novel insights into 
      the arsenical immunotoxicity and provide a basis for the preve.ntive and 
      therapeutic potential of PINK1/Parkin-mediated mitophagy in arsenic poisoning.
FAU - Qu, Gaoyang
AU  - Qu G
AD  - Hebei Key Laboratory for Organ Fibrosis Research, School of Public Health, North 
      China University of Science and Technology, Tangshan 063210, China.
FAU - Liu, Zi
AU  - Liu Z
AD  - Hebei Key Laboratory for Organ Fibrosis Research, School of Public Health, North 
      China University of Science and Technology, Tangshan 063210, China.
FAU - Zhang, Jiaxin
AU  - Zhang J
AD  - Hebei Key Laboratory for Organ Fibrosis Research, School of Public Health, North 
      China University of Science and Technology, Tangshan 063210, China.
FAU - Guo, Yaning
AU  - Guo Y
AD  - Hebei Key Laboratory for Organ Fibrosis Research, School of Public Health, North 
      China University of Science and Technology, Tangshan 063210, China.
FAU - Li, Hui
AU  - Li H
AD  - Hebei Key Laboratory for Organ Fibrosis Research, School of Public Health, North 
      China University of Science and Technology, Tangshan 063210, China.
FAU - Qu, Ruijie
AU  - Qu R
AD  - Hebei Key Laboratory for Organ Fibrosis Research, School of Public Health, North 
      China University of Science and Technology, Tangshan 063210, China.
FAU - Su, Wei
AU  - Su W
AD  - Hebei Key Laboratory for Organ Fibrosis Research, School of Public Health, North 
      China University of Science and Technology, Tangshan 063210, China.
FAU - Zhang, Huan
AU  - Zhang H
AD  - Hebei Key Laboratory for Organ Fibrosis Research, School of Public Health, North 
      China University of Science and Technology, Tangshan 063210, China.
FAU - Zhang, Lin
AU  - Zhang L
AD  - Department of Internal Medicine Nursing, School of Nursing, Wannan Medical 
      College, Wuhu 241000, China.
FAU - Xu, Hong
AU  - Xu H
AUID- ORCID: 0000-0002-3655-3833
AD  - Hebei Key Laboratory for Organ Fibrosis Research, School of Public Health, North 
      China University of Science and Technology, Tangshan 063210, China.
FAU - Shen, Fuhai
AU  - Shen F
AD  - Hebei Key Laboratory for Organ Fibrosis Research, School of Public Health, North 
      China University of Science and Technology, Tangshan 063210, China.
FAU - Jiang, Shoufang
AU  - Jiang S
AD  - Hebei Key Laboratory for Organ Fibrosis Research, School of Public Health, North 
      China University of Science and Technology, Tangshan 063210, China.
FAU - Liu, Heliang
AU  - Liu H
AD  - Hebei Key Laboratory for Organ Fibrosis Research, School of Public Health, North 
      China University of Science and Technology, Tangshan 063210, China.
FAU - Li, Jinlong
AU  - Li J
AUID- ORCID: 0000-0002-5332-6659
AD  - Hebei Key Laboratory for Organ Fibrosis Research, School of Public Health, North 
      China University of Science and Technology, Tangshan 063210, China.
LA  - eng
GR  - H2019209576/Natural Science Foundation of Hebei Province/
GR  - JQN2019012/Basic Research Program of Science and Technology in Education De- 408 
      partment of Hebei Province/
GR  - 82003404/National Natural Science Foundation of China (NSFC)/
PT  - Journal Article
DEP - 20221213
PL  - Switzerland
TA  - Molecules
JT  - Molecules (Basel, Switzerland)
JID - 100964009
RN  - N712M78A8G (Arsenic)
RN  - EC 2.7.- (Protein Kinases)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - 207137-56-2 (Interleukin-4)
RN  - 0 (Interleukin-6)
RN  - 0 (Arsenicals)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
SB  - IM
MH  - Mice
MH  - Animals
MH  - Mitophagy
MH  - *Arsenic/toxicity
MH  - Protein Kinases/metabolism
MH  - Hydrogen Peroxide/pharmacology
MH  - Interleukin-4/pharmacology
MH  - Interleukin-6/pharmacology
MH  - Kupffer Cells/metabolism
MH  - Liver/metabolism
MH  - *Arsenicals
MH  - Ubiquitin-Protein Ligases/genetics/metabolism
PMC - PMC9780783
OTO - NOTNLM
OT  - PINK1
OT  - arsenic
OT  - immunotoxicity
OT  - liver
OT  - macrophage
OT  - mitophagy
COIS- The authors declare no conflict of interest.
EDAT- 2022/12/24 06:00
MHDA- 2022/12/27 06:00
PMCR- 2022/12/13
CRDT- 2022/12/23 01:49
PHST- 2022/11/07 00:00 [received]
PHST- 2022/11/28 00:00 [revised]
PHST- 2022/12/10 00:00 [accepted]
PHST- 2022/12/23 01:49 [entrez]
PHST- 2022/12/24 06:00 [pubmed]
PHST- 2022/12/27 06:00 [medline]
PHST- 2022/12/13 00:00 [pmc-release]
AID - molecules27248862 [pii]
AID - molecules-27-08862 [pii]
AID - 10.3390/molecules27248862 [doi]
PST - epublish
SO  - Molecules. 2022 Dec 13;27(24):8862. doi: 10.3390/molecules27248862.