Acute cadmium chloride administration induces hepatic and renal CYP2A5 mRNA, protein and activity in the mouse: involvement of transcription factor NRF2

Abu-Bakar, A’edah, Satarug, Soisungwan, Marks, Geoffrey C., Lang, Matti A. and Moore, Michael R. (2004) Acute cadmium chloride administration induces hepatic and renal CYP2A5 mRNA, protein and activity in the mouse: involvement of transcription factor NRF2. Toxicology Letters, 148 3: 199-210.


Author Abu-Bakar, A’edah
Satarug, Soisungwan
Marks, Geoffrey C.
Lang, Matti A.
Moore, Michael R.
Title Acute cadmium chloride administration induces hepatic and renal CYP2A5 mRNA, protein and activity in the mouse: involvement of transcription factor NRF2
Journal name Toxicology Letters   Check publisher's open access policy
ISSN 0378-4274
Publication date 2004-01-15
Sub-type Article (original research)
DOI 10.1016/j.toxlet.2003.10.029
Volume 148
Issue 3
Start page 199
End page 210
Total pages 12
Place of publication Clare, Ireland
Publisher Elsevier Sci Ireland
Language eng
Subject 11 Medical and Health Sciences
1107 Immunology
Abstract Modulation of the cytochrome P450 (CYP) monooxygenase system by cadmium was investigated in male, adult DBA/2J mice treated with a single dose (16 mumol/kg body weight, i.p.) of cadmium chloride (CdCl2). Total CYP content of liver and kidney microsomes decreased maximally (56% and 85%, respectively) 24 and 18 h, respectively, after CdCl2 treatment. Progressive increases of hepatic coumarin 7-hydroxylase (COH) activity; indicative of CYP2A5 activity, relative to the total CYP content were seen at 8 h (2-fold), 12 h (3-fold), 18 h (12-fold), and 24 h (15-fold). Similar changes were seen in the kidney. Liver and kidney CYP2A5 mRNA levels increased maximally 12 and 4 h after treatment and decreased to almost half 6 h later. In contrast, kidney and liver CYP2A5 protein levels increased maximally at 18 and 24 h. The CYP2A5 mRNA levels in the kidney and liver increased after Cd treatment in Nrf2 +/+ but not in Nrf2 -/- mouse. This study demonstrates that hepatic and kidney CYP2A5 is upregulated by cadmium with a somewhat faster response in the kidney than the liver. The strong upregulation of the CYP2A5 both at mRNA and enzyme activity levels, with a simultaneous decrease in the total CYP concentration suggest an unusual mode of regulation of CYP2A5 in response to cadmium exposure, amongst the CYP enzymes. The observed decrease in the mRNA but not in protein levels after maximal induction may suggest involvement of post-trancriptional mechanisms in the regulation. Upregulation of CYP2A5 by cadmium in the Nrf2 +/+ mice but not in the Nrf2 -/- mice indicates a role for this transcription factor in the regulation. (C) 2003 Elsevier Ireland Ltd. All rights reserved.
Keyword Cadmium
Cytochrome P450 2a5
Coumarin 7-hydroxylase
Nrf2
Stress response gene
Heme oxygenase
Posttranscriptional regulation
Mammalian-cells
Liver
Induction
Gene
Pyrazole
Expression
Cytochrome-p-450
Toxicology
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
National Research Centre for Environmental Toxicology Publications
 
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