HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 280, Issue 28, 26193-26199, July 15, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/28/26193    most recent M501371200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Li, C.-H. Articles by Kang, J.-J. Search for Related Content PubMed PubMed Citation Articles by Li, C.-H. Articles by Kang, J.-J. Social Bookmarking                      What's this?

Chloramphenicol-induced Mitochondrial Stress Increases p21 Expression and Prevents Cell Apoptosis through a p21-dependent Pathway^*

Ching-Hao Li, Su-Liang Tzeng, Yu-Wen Cheng, and Jaw-Jou Kang

From the Institute of Toxicology, College of Medicine, National Taiwan University, Taipei 100, Taiwan

Pretreatment of HepG2 and H1299 cells with chloramphenicol rendered the cells resistant to mitomycin-induced apoptosis. Both mitomycin-induced caspase 3 activity and PARP activation were also inhibited. The mitochondrial DNA-encoded Cox I protein, but not nuclear-encoded proteins, was down-regulated in chloramphenicol-treated cells. Cellular levels of the p21^waf1/cip1 protein and p21^waf1/cip1 mRNA were increased through a p53-independent pathway, possibly because of the stabilization of p21^waf1/cip1 mRNA in chloramphenicol-treated cells. The p21^waf1/cip1 was redistributed from the perinuclear region to the cytoplasm and co-localized with mitochondrial marker protein. Several morphological changes and activation of the senescence-associated biomarker, SA -galactosidase, were observed in these cells. Both p21^waf1/cip1 antisense and small interfering RNA could restore apoptotic-associated caspase 3 activity, PARP activation, and sensitivity to mitomycin-induced apoptosis. Similar effects were seen with other antibiotics that inhibit mitochondrial translation, including minocycline, doxycycline, and clindamycin. These findings suggested that mitochondrial stress causes resistance to apoptosis through a p21-dependent pathway.

Received for publication, February 4, 2005 , and in revised form, April 11, 2005.

^* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed: Institute of Toxicology, College of Medicine, National Taiwan University, No. 1 Jen-Ai Rd., Section 1, Taipei 100, Taiwan. Tel.: 886-2-23123456 (ext. 8603); Fax: 886-2-23410217; E-mail: jjkang{at}ha.mc.ntu.edu.tw.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				L. Khidr, G. Wu, A. Davila, V. Procaccio, D. Wallace, and W.-H. Lee Role of SUV3 Helicase in Maintaining Mitochondrial Homeostasis in Human Cells J. Biol. Chem., October 3, 2008; 283(40): 27064 - 27073. [Abstract] [Full Text] [PDF]

				E. Crescenzi, G. Palumbo, J. de Boer, and H. J.M. Brady Ataxia Telangiectasia Mutated and p21CIP1 Modulate Cell Survival of Drug-Induced Senescent Tumor Cells: Implications for Chemotherapy Clin. Cancer Res., March 15, 2008; 14(6): 1877 - 1887. [Abstract] [Full Text] [PDF]

				C. Harms, K. Albrecht, U. Harms, K. Seidel, L. Hauck, T. Baldinger, D. Hubner, G. Kronenberg, J. An, K. Ruscher, et al. Phosphatidylinositol 3-Akt-Kinase-Dependent Phosphorylation of p21Waf1/Cip1 as a Novel Mechanism of Neuroprotection by Glucocorticoids J. Neurosci., April 25, 2007; 27(17): 4562 - 4571. [Abstract] [Full Text] [PDF]

				H. Li, X. Wang, N. Li, J. Qiu, Y. Zhang, and X. Cao hPEBP4 Resists TRAIL-induced Apoptosis of Human Prostate Cancer Cells by Activating Akt and Deactivating ERK1/2 Pathways J. Biol. Chem., February 16, 2007; 282(7): 4943 - 4950. [Abstract] [Full Text] [PDF]

				S.-L. Tzeng, Y.-W. Cheng, C.-H. Li, Y.-S. Lin, H.-C. Hsu, and J.-J. Kang Physiological and Functional Interactions between Tcf4 and Daxx in Colon Cancer Cells J. Biol. Chem., June 2, 2006; 281(22): 15405 - 15411. [Abstract] [Full Text] [PDF]

				J. Pei, J. E. Turse, Q. Wu, and T. A. Ficht Brucella abortus Rough Mutants Induce Macrophage Oncosis That Requires Bacterial Protein Synthesis and Direct Interaction with the Macrophage. Infect. Immun., May 1, 2006; 74(5): 2667 - 2675. [Abstract] [Full Text] [PDF]