Characterization of Cd-induced molecular events prior to cellular damage in primary rat hepatocytes in culture: activation of the stress activated signal protein JNK and transcription factor AP-1

Journal of Biochemical and Molecular Toxicology
Chin-ju J Hsiao, Susan R Stapleton

Abstract

The effect of Cadmium (Cd) on the expression of c-Jun N-terminal kinase (JNK), c-jun, and activator protein-1 (AP-1) has been investigated. We previously reported that Cd causes cell damage as indicated by increases in the cytotoxic parameters, lactate dehydrogenase and lipid peroxidation, and this damage was mediated by decreases in cellular concentration of glutathione. In the present study, we investigate the molecular events involved prior to the Cd-induced cellular toxicity and damage in primary rat hepatocytes. We propose that Cd, through the generation of reactive oxygen species (ROS) and prior to significant cellular damage, activates the stress activated signal protein JNK, regulates c-jun expression, and promotes the binding of a redox sensitive transcription factor AP-1. We show JNK activity and c-jun mRNA level significantly increased at 1 h and AP-1 DNA binding activity significantly enhanced at 3 h in the presence of 4 microM cadmium chloride. Blocking the Cd induction of JNK activity, c-jun mRNA level, and AP-1 binding activity using the antioxidants N-acetyl cysteine (10 mM) or carnosol (0.5 microg/mL) suggests a role for ROS. Blocking JNK activity and c-jun mRNA by SP600125 (20 microM), a JNK inhibitor, support...Continue Reading

References

Jul 14, 1995·The Journal of Biological Chemistry·M Karin
Apr 1, 1997·Current Opinion in Cell Biology·M KarinE Zandi
Jul 10, 1999·The Journal of Biological Chemistry·V Moreno-ManzanoM Kitamura
Aug 13, 1999·Toxicological Sciences : an Official Journal of the Society of Toxicology·A R ParrishA J Gandolfi
Jan 19, 2000·Toxicology and Applied Pharmacology·W Ding, D M Templeton
Nov 15, 2000·American Journal of Physiology. Lung Cellular and Molecular Physiology·V J Thannickal, B L Fanburg
Mar 27, 2001·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·P DebersacM H Siess
Apr 24, 2001·Pharmacology & Therapeutics·S K Wattanapitayakul, J A Bauer
Feb 2, 2002·Nature Reviews. Molecular Cell Biology·Catherine A Hazzalin, Louis C Mahadevan
May 30, 2002·Cellular Signalling·Eva RajnavolgyiScott K Durum
Jul 19, 2002·Biochemical Pharmacology·David Andrés, María Cascales
Sep 3, 2002·Toxicology·Elisabetta CasalinoClemente Landriscina
Apr 2, 2003·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Robert F SchwabeDavid A Brenner
Apr 30, 2003·Journal of Biochemical and Molecular Toxicology·Jun XuSusan R Stapleton
May 30, 2003·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Mark J CzajaYongjun Wang
Jul 16, 2003·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Irina Vasilevskaya, Peter J O'Dwyer
Jul 25, 2003·Biochemical and Biophysical Research Communications·Dhara VaishnavSubbiah Pugazhenthi
Sep 6, 2003·Free Radical Biology & Medicine·Philippe BécuweMichel Dauça

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Citations

Aug 29, 2013·Archives of Toxicology·Frank Thévenod, Wing-Kee Lee
Jun 23, 2011·PloS One·Brooke E TvermoesJonathan H Freedman
Oct 13, 2009·Toxicology Mechanisms and Methods·Ma del Carmen EscobarMa Concepción Gutiérrez Ruiz
May 12, 2009·Toxicology Letters·Verónica SouzaMa Concepción Gutiérrez Ruiz
Jan 22, 2009·Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP·Laura VerganiGabriella Gallo
Nov 18, 2008·Biochimie·Chin-ju J Hsiao, Susan R Stapleton
Feb 3, 2007·Toxicology Letters·Neelima Pathak, Shashi Khandelwal
Apr 26, 2006·Journal of Pineal Research·C Martínez-CampaE J Sánchez-Barceló
Oct 10, 2006·Molecular and Cellular Endocrinology·Laura VerganiGabriella Gallo
Feb 15, 2019·Journal of Animal Physiology and Animal Nutrition·Heba S A TahaMahmoud Alagawany
Jun 30, 2005·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Pham T N DiepCatherine Jumarie

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