Reactive oxygen species-induced cell death of rat primary astrocytes through mitochondria-mediated mechanism

Chia Chun Wang, Kuan Min Fang, Chung Shi Yang, Shun-Fen Tzeng

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Astrocytes, the most abundant glial cell population in the central nervous system (CNS), play physiological roles in neuronal activities. Oxidative insult induced by the injury to the CNS causes neural cell death through extrinsic and intrinsic pathways. This study reports that reactive oxygen species (ROS) generated by exposure to the strong oxidizing agent, hexavalent chromium (Cr(VI)) as a chemical-induced oxidative stress model, caused astrocytes to undergo an apoptosis-like cell death through a caspase-3-independent mechanism. Although activating protein-1 (AP-1) and NF-κB were activated in Cr(VI)-primed astrocytes, the inhibition of their activity failed to increase astrocytic cell survival. The results further indicated that the reduction in mitochondrial membrane potential (MMP) was accompanied by an increase in the levels of ROS in Cr(VI)-primed astrocytes. Moreover, pretreatment of astrocytes with N-acetylcysteine (NAC), the potent ROS scavenger, attenuated ROS production and MMP loss in Cr(VI)-primed astrocytes, and significantly increased the survival of astrocytes, implying that the elevated ROS disrupted the mitochondrial function to result in the reduction of astrocytic cell viability. In addition, the nuclear expression of apoptosis-inducing factor (AIF) and endonuclease G (EndoG) was observed in Cr(VI)-primed astrocytes. Taken together, evidence shows that astrocytic cell death occurs by ROS-induced oxidative insult through a caspase-3-independent apoptotic mechanism involving the loss of MMP and an increase in the nuclear levels of mitochondrial pro-apoptosis proteins (AIF/EndoG). This mitochondria-mediated but caspase-3-independent apoptotic pathway may be involved in oxidative stress-induced astrocytic cell death in the injured CNS.

Original languageEnglish
Pages (from-to)933-943
Number of pages11
JournalJournal of Cellular Biochemistry
Volume107
Issue number5
DOIs
Publication statusPublished - 2009 Aug 1

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Mitochondria
Cell death
Astrocytes
Rats
Reactive Oxygen Species
Cell Death
Mitochondrial Membrane Potential
Neurology
Caspase 3
Apoptosis Inducing Factor
Oxidative stress
Central Nervous System
Membranes
Cell Survival
Oxidative Stress
Neurofibromin 1
Cells
Apoptosis
Acetylcysteine
chromium hexavalent ion

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

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abstract = "Astrocytes, the most abundant glial cell population in the central nervous system (CNS), play physiological roles in neuronal activities. Oxidative insult induced by the injury to the CNS causes neural cell death through extrinsic and intrinsic pathways. This study reports that reactive oxygen species (ROS) generated by exposure to the strong oxidizing agent, hexavalent chromium (Cr(VI)) as a chemical-induced oxidative stress model, caused astrocytes to undergo an apoptosis-like cell death through a caspase-3-independent mechanism. Although activating protein-1 (AP-1) and NF-κB were activated in Cr(VI)-primed astrocytes, the inhibition of their activity failed to increase astrocytic cell survival. The results further indicated that the reduction in mitochondrial membrane potential (MMP) was accompanied by an increase in the levels of ROS in Cr(VI)-primed astrocytes. Moreover, pretreatment of astrocytes with N-acetylcysteine (NAC), the potent ROS scavenger, attenuated ROS production and MMP loss in Cr(VI)-primed astrocytes, and significantly increased the survival of astrocytes, implying that the elevated ROS disrupted the mitochondrial function to result in the reduction of astrocytic cell viability. In addition, the nuclear expression of apoptosis-inducing factor (AIF) and endonuclease G (EndoG) was observed in Cr(VI)-primed astrocytes. Taken together, evidence shows that astrocytic cell death occurs by ROS-induced oxidative insult through a caspase-3-independent apoptotic mechanism involving the loss of MMP and an increase in the nuclear levels of mitochondrial pro-apoptosis proteins (AIF/EndoG). This mitochondria-mediated but caspase-3-independent apoptotic pathway may be involved in oxidative stress-induced astrocytic cell death in the injured CNS.",
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Reactive oxygen species-induced cell death of rat primary astrocytes through mitochondria-mediated mechanism. / Wang, Chia Chun; Fang, Kuan Min; Yang, Chung Shi; Tzeng, Shun-Fen.

In: Journal of Cellular Biochemistry, Vol. 107, No. 5, 01.08.2009, p. 933-943.

Research output: Contribution to journalArticle

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