Tags

Type your tag names separated by a space and hit enter

Oxidative stress induces parallel autophagy and mitochondria dysfunction in human glioma U251 cells.
Toxicol Sci 2009; 110(2):376-88TS

Abstract

Accumulation of reactive oxygen species (ROS) such as hydrogen peroxide (H(2)O(2)) is an oxidative stress response, which induced various defense mechanisms or programmed cell death (PCD). As one of the major types of PCD, 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 ROS regulates autophagy is still poorly understood. Thus, the purposes of this study were to elucidate how H(2)O(2) exerts its cytotoxic effects on malignant glioma U251 cells and to uncover the molecular mechanism that might be involved. Here, we show that H(2)O(2)-induced autophagy and apoptosis in U251 cells are mediated through 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 through both the Beclin 1 and the 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 H(2)O(2) 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.

Authors+Show Affiliations

Department of Pathophysiology, Norman Bethune College of Medicine, Jilin University, Changchun, Jilin 130021, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19451193

Citation

Zhang, Hongyu, et al. "Oxidative Stress Induces Parallel Autophagy and Mitochondria Dysfunction in Human Glioma U251 Cells." Toxicological Sciences : an Official Journal of the Society of Toxicology, vol. 110, no. 2, 2009, pp. 376-88.
Zhang H, Kong X, Kang J, et al. Oxidative stress induces parallel autophagy and mitochondria dysfunction in human glioma U251 cells. Toxicol Sci. 2009;110(2):376-88.
Zhang, H., Kong, X., Kang, J., Su, J., Li, Y., Zhong, J., & Sun, L. (2009). Oxidative stress induces parallel autophagy and mitochondria dysfunction in human glioma U251 cells. Toxicological Sciences : an Official Journal of the Society of Toxicology, 110(2), pp. 376-88. doi:10.1093/toxsci/kfp101.
Zhang H, et al. Oxidative Stress Induces Parallel Autophagy and Mitochondria Dysfunction in Human Glioma U251 Cells. Toxicol Sci. 2009;110(2):376-88. PubMed PMID: 19451193.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Oxidative stress induces parallel autophagy and mitochondria dysfunction in human glioma U251 cells. AU - Zhang,Hongyu, AU - Kong,Xiaoxia, AU - Kang,Jinsong, AU - Su,Jing, AU - Li,Yang, AU - Zhong,Jiateng, AU - Sun,Liankun, Y1 - 2009/05/18/ PY - 2009/5/20/entrez PY - 2009/5/20/pubmed PY - 2009/9/18/medline SP - 376 EP - 88 JF - Toxicological sciences : an official journal of the Society of Toxicology JO - Toxicol. Sci. VL - 110 IS - 2 N2 - Accumulation of reactive oxygen species (ROS) such as hydrogen peroxide (H(2)O(2)) is an oxidative stress response, which induced various defense mechanisms or programmed cell death (PCD). As one of the major types of PCD, 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 ROS regulates autophagy is still poorly understood. Thus, the purposes of this study were to elucidate how H(2)O(2) exerts its cytotoxic effects on malignant glioma U251 cells and to uncover the molecular mechanism that might be involved. Here, we show that H(2)O(2)-induced autophagy and apoptosis in U251 cells are mediated through 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 through both the Beclin 1 and the 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 H(2)O(2) 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. SN - 1096-0929 UR - https://www.unboundmedicine.com/medline/citation/19451193/Oxidative_stress_induces_parallel_autophagy_and_mitochondria_dysfunction_in_human_glioma_U251_cells_ L2 - https://academic.oup.com/toxsci/article-lookup/doi/10.1093/toxsci/kfp101 DB - PRIME DP - Unbound Medicine ER -