Skip Navigation



ToxSci Advance Access published online on May 18, 2009
Toxicological Sciences, doi:10.1093/toxsci/kfp101
This Article
Right arrow Advance Access manuscript (PDF)
Right arrow All Versions of this Article:
110/2/376    most recent
kfp101v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Zhang, H.
Right arrow Articles by Sun, L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zhang, H.
Right arrow Articles by Sun, L.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2009. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

Oxidative stress induces parallel autophagy and mitochondria dysfunction in human glioma U251 cells

Hongyu Zhang, Xiaoxia Kong, Jinsong Kang, Jing Su, Yang Li, Jiateng Zhong and Liankun Sun1

Department of Pathophysiology, Norman Bethune College of Medicine, Jilin University, 2 Xinmin Street, Changchun, Jilin, 130021, China

1 To whom correspondence should be addressed at Department of Pathophysiology, Norman Bethune College of Medicine, Jilin University, Changchun, Jilin, 130021, China. Fax: 86-431-85619402. E-mail: sunlk{at}jlu.edu.cn

Received February 14, 2009; revision received May 7, 2009; accepted May 8, 2009


  Abstract

Accumulation of reactive oxygen species (ROS) such as Hydrogen peroxide (H2O2), is an oxidative stress response induced various defense mechanisms or program cell death (PCD). As one of the major types of program cell death, autophagy has been observed in response to several anticancer drugs and demonstrated to be responsible for cell death. To date, however, the exact mechanism by which reactive oxygen species regulate autophagy is still poorly understood. Thus the purpose of this study was to elucidate how H2O2 exerts its cytotoxic effects on malignant glioma U251 cells, and to uncover the molecular mechanism that might be involved. Here we show that H2O2 induced autophagy and apoptosis in U251 cells, is mediated though the Beclin 1 and Akt/mTOR pathways. Accumulation of ROS leads to changes in mitochondrial permeability with loss of mitochondrial membrane potential, and disruption of mitochondrial dynamics at a transcriptional level of fission and fusion. Overexpression of cellular Bcl-2 partially inhibited autophagy though both the Beclin 1 and Akt/mTOR pathways, and led to recovery of mitochondrial dynamics. When autophagy was prevented at an early stage by 3-methyladenine, apoptosis significantly increased. Our data provide the first evidence that H2O2 induces autophagy through interference with the Beclin 1 and Akt/mTOR signaling pathways, and is regulated by the anti-apoptotic gene Bcl-2 in glioma U251 cells.

Key Words: Autophagy; Mitochondria; Bcl-2; PI3K/Akt/mTOR; Apoptosis.

Hong-yu Zhang and Xiao-xia Kong contributed equally to this paper.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.