Intracellular glutathione levels are involved in carbonyl cyanide p-(trifluoromethoxy) phenylhydrazone-induced apoptosis in As4.1 juxtaglomerular cells

  • Authors:
    • Yong Hwan Han
    • Woo Hyun Park
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  • Published online on: January 21, 2011     https://doi.org/10.3892/ijmm.2011.604
  • Pages: 575-581
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Abstract

Carbonyl cyanide p-(trifluoromethoxy) phenylhydrazone (FCCP) is an uncoupler of mitochondrial oxidative phosphorylation in eukaryotic cells. In the present study, we investigated the involvement of reactive oxygen species (ROS) and glutathione (GSH) in FCCP-induced As4.1 juxtaglomerular cell death. Intracellular ROS levels were decreased by FCCP at the early time points (10-150 min) and increased at 48 h. FCCP inhibited the activity of Mn-superoxide dismutase (Mn-SOD) via down-regulating its protein expression. Ebselen (an antioxidant) significantly attenuated ROS levels in FCCP-treated cells, but did not prevent FCCP-induced cell death. Moreover, intracellular GSH content was rapidly diminished within 10 min of FCCP treatment, which was accompanied by a reduction of the mitochondrial membrane potential [MMP (∆ψm)]. L-buthionine sulfoximine (BSO, a GSH synthesis inhibitor) significantly augmented As4.1 cell death by FCCP. However, N-acetylcysteine (NAC, a GSH precursor and antioxidant) attenuated GSH depletion, MMP (∆ψm) loss and cell death in FCCP-treated As4.1 cells. In addition, NAC increased Mn-SOD activity and decreased ROS levels in FCCP-treated As4.1 cells. In conclusion, these results suggest that compared to ROS levels, intracellular GSH levels are more closely linked to FCCP-induced apoptosis in As4.1 juxtaglomerular cells.

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April 2011
Volume 27 Issue 4

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Han YH and Han YH: Intracellular glutathione levels are involved in carbonyl cyanide p-(trifluoromethoxy) phenylhydrazone-induced apoptosis in As4.1 juxtaglomerular cells. Int J Mol Med 27: 575-581, 2011
APA
Han, Y.H., & Han, Y.H. (2011). Intracellular glutathione levels are involved in carbonyl cyanide p-(trifluoromethoxy) phenylhydrazone-induced apoptosis in As4.1 juxtaglomerular cells. International Journal of Molecular Medicine, 27, 575-581. https://doi.org/10.3892/ijmm.2011.604
MLA
Han, Y. H., Park, W. H."Intracellular glutathione levels are involved in carbonyl cyanide p-(trifluoromethoxy) phenylhydrazone-induced apoptosis in As4.1 juxtaglomerular cells". International Journal of Molecular Medicine 27.4 (2011): 575-581.
Chicago
Han, Y. H., Park, W. H."Intracellular glutathione levels are involved in carbonyl cyanide p-(trifluoromethoxy) phenylhydrazone-induced apoptosis in As4.1 juxtaglomerular cells". International Journal of Molecular Medicine 27, no. 4 (2011): 575-581. https://doi.org/10.3892/ijmm.2011.604