| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1 Department of Medicine and Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, New York 10461; and 2 Departments of Medicine and Biochemistry and Biophysics, Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, North Carolina 27599
To determine whether intracellular signaling events involved in apoptosis may also mediate necrosis, the role of the transcription factor AP-1 was investigated in a hepatoma cell model of cellular necrosis induced by oxidant stress. Treatment of the human hepatoma cell line HuH-7 with H2O2 caused dose-dependent necrosis as determined by light microscopy, fluorescent staining, and an absence of DNA fragmentation. H2O2 treatment led to increases in c-fos and c-jun mRNA levels, Jun nuclear kinase activity, and AP-1 DNA binding. AP-1 transcriptional activity measured with an AP-1-driven luciferase reporter gene was also increased. To determine whether this AP-1 activation contributed to H2O2-induced cell necrosis, HuH-7 cells were stably transfected with an antisense c-jun expression vector. Cells expressing antisense c-jun had decreased levels of AP-1 activation and significantly increased survival after H2O2 exposure. These data indicate that AP-1 activation occurs during oxidant-induced cell necrosis and contributes to cell death. Necrosis is therefore not always a passive process but may involve the activation of intracellular signaling pathways similar to those that mediate apoptosis.
c-fos; c-jun; apoptosis; hepatoma cell
This article has been cited by other articles:
|
|
 |
|
  M. J. Czaja The Future of GI and Liver Research: Editorial Perspectives: III. JNK/AP-1 regulation of hepatocyte death Am J Physiol Gastrointest Liver Physiol, June 1, 2003; 284(6): G875 - G879. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Streetz, B. Fregien, J. Plumpe, K. Korber, S. Kubicka, G. Sass, S. C. Bischoff, M. P. Manns, G. Tiegs, and C. Trautwein Dissection of the Intracellular Pathways in Hepatocytes Suggests a Role for Jun Kinase and IFN Regulatory Factor-1 in Con A-Induced Liver Failure J. Immunol., July 1, 2001; 167(1): 514 - 523. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. E. Jones, C. R. Lo, H. Liu, Z. Pradhan, L. Garcia, A. Srinivasan, K. L. Valentino, and M. J. Czaja Role of caspases and NF-kappa B signaling in hydrogen peroxide- and superoxide-induced hepatocyte apoptosis Am J Physiol Gastrointest Liver Physiol, May 1, 2000; 278(5): G693 - G699. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. M. Manzano, M. R. Puyol, D. R. Puyol, and F. J. L. Cazaña Tretinoin Prevents Age-Related Renal Changes and Stimulates Antioxidant Defenses in Cultured Renal Mesangial Cells J. Pharmacol. Exp. Ther., April 1, 1999; 289(1): 123 - 132. [Abstract] [Full Text]
|
|
|
|
 |
|
 T. Minamoto, M. Mai, and Z.'e. Ronai Environmental factors as regulators and effectors of multistep carcinogenesis Carcinogenesis, April 1, 1999; 20(4): 519 - 527. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. E. Jones and M. J. Czaja III. Intracellular signaling in response to toxic liver injury Am J Physiol Gastrointest Liver Physiol, November 1, 1998; 275(5): G874 - G878. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Liu, C. R. Lo, B. E. Jones, Z. Pradhan, A. Srinivasan, K. L. Valentino, R. J. Stockert, and M. J. Czaja Inhibition of c-Myc Expression Sensitizes Hepatocytes to Tumor Necrosis Factor-induced Apoptosis and Necrosis J. Biol. Chem., December 15, 2000; 275(51): 40155 - 40162. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
