PMID- 36245390
OWN - NLM
STAT- MEDLINE
DCOM- 20230213
LR  - 20230213
IS  - 1099-0461 (Electronic)
IS  - 1095-6670 (Linking)
VI  - 37
IP  - 2
DP  - 2023 Feb
TI  - Mercury and methylmercury differentially modulate hepatic cytochrome P450 1A1 and 
      1A2 in vivo and in vitro.
PG  - e23243
LID - 10.1002/jbt.23243 [doi]
AB  - The cytochrome P450 1 A (CYP1A) subfamily enzymes are involved in the metabolic 
      activation of several xenobiotics to toxic metabolites and reactive 
      intermediates, resulting ultimately in carcinogenesis. Mercury and halogenated 
      aromatic hydrocarbons (HAHs), typified by 2,3,7,8-tetrachlorodibenzo-p-dioxin 
      (TCDD), are persistent environmental pollutants involved in the modulation of 
      aryl hydrocarbon receptor (AHR) gene battery, including cytochrome P450 (CYP) 
      genes. We previously investigated the effect of coexposure to either inorganic or 
      organic mercury (Hg(+2) and MeHg) with TCDD on CYP1A1 in vitro. Thus, we examined 
      the impact of coexposure to Hg(+2) or MeHg and TCDD on AHR-regulated genes 
      (Cyp1a1/1a2) in vivo and in vitro. Therefore, male C57BL/6 mice were injected 
      intraperitoneally with MeHg or Hg(+2) (2.5 mg/kg) in the absence and presence of 
      TCDD (15 mug/kg) for 6 or 24 h. The concentration-dependent effect of MeHg was 
      examined in murine hepatoma Hepa1c1c7 cells. In vivo, both MeHg and Hg(2+) 
      inhibited the TCDD-mediated induction of Cyp1a1/1a2 mRNA levels. However, Only 
      Hg(2+) was able to inhibit the TCDD-mediated induction at posttranscriptional 
      levels of CYP1A1/1A2 protein and catalytic activity, suggesting differential 
      modulation effects by Hg(+2) and MeHg. In addition, the inhibitory role of HO-1 
      (Heme oxygenase-1) on CYP1A activity induced by TCDD was investigated using a 
      HO-1 competitive inhibitor, tin-mesoporphyrin, that partially restored the 
      MeHg-mediated decrease in CYP1A1 activity. This study demonstrates that MeHg, 
      alongside Hg(2+) , can differentially modulate the TCDD-induced AHR-regulated 
      genes (Cyp1a1/1a2) at different expression levels in C57BL/6 mice liver and 
      Hepa1c1c7 cells.
CI  - (c) 2022 Wiley Periodicals LLC.
FAU - Alqahtani, Mohammed A
AU  - Alqahtani MA
AD  - Department of Pharmaceutical Sciences, 2142 J Katz Group-Rexall Centre for 
      Pharmacy and Health Research Edmonton, University of Alberta Ringgold Standard 
      Institution, Edmonton, Alberta, Canada.
FAU - El-Ghiaty, Mahmoud A
AU  - El-Ghiaty MA
AD  - Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, 
      Alberta, Canada.
FAU - El-Kadi, Ayman O S
AU  - El-Kadi AOS
AUID- ORCID: 0000-0002-8692-0400
AD  - Faculty of Pharmacy and Pharmaceutical Sciences, 2142 J Katz Group-Rexall Centre 
      for Pharmacy and Health Research, University of Alberta, Edmonton, Alberta, 
      Canada.
LA  - eng
GR  - Discovery Grant RGPIN 250139-17/Natural Sciences and Engineering Research Council 
      of Canada/
PT  - Journal Article
DEP - 20221017
PL  - United States
TA  - J Biochem Mol Toxicol
JT  - Journal of biochemical and molecular toxicology
JID - 9717231
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP1A1)
RN  - 0 (Methylmercury Compounds)
RN  - FXS1BY2PGL (Mercury)
RN  - 9035-51-2 (Cytochrome P-450 Enzyme System)
RN  - 0 (Polychlorinated Dibenzodioxins)
RN  - 0 (Receptors, Aryl Hydrocarbon)
SB  - IM
MH  - Male
MH  - Mice
MH  - Animals
MH  - Cytochrome P-450 CYP1A1/genetics
MH  - *Methylmercury Compounds/toxicity/metabolism
MH  - *Mercury/toxicity/metabolism
MH  - Mice, Inbred C57BL
MH  - Liver/metabolism
MH  - Cytochrome P-450 Enzyme System/metabolism
MH  - *Polychlorinated Dibenzodioxins/toxicity
MH  - Receptors, Aryl Hydrocarbon/metabolism
OTO - NOTNLM
OT  - AHR
OT  - CYP1A
OT  - carcinogenesis
OT  - dioxin
OT  - mercury
EDAT- 2022/10/18 06:00
MHDA- 2023/02/14 06:00
CRDT- 2022/10/17 04:04
PHST- 2022/08/16 00:00 [revised]
PHST- 2021/10/20 00:00 [received]
PHST- 2022/10/06 00:00 [accepted]
PHST- 2022/10/18 06:00 [pubmed]
PHST- 2023/02/14 06:00 [medline]
PHST- 2022/10/17 04:04 [entrez]
AID - 10.1002/jbt.23243 [doi]
PST - ppublish
SO  - J Biochem Mol Toxicol. 2023 Feb;37(2):e23243. doi: 10.1002/jbt.23243. Epub 2022 
      Oct 17.