Γ-H2AX Formation is not Coupled to Elevations in Intracellular Ca2+, and Hyperactivation of PARP does not Facilitate AIF Translocation During ROS-induced Cell Death

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	Γ-H2AX Formation is not Coupled to Elevations in Intracellular Ca2+, and Hyperactivation of PARP does not Facilitate AIF Translocation During ROS-induced Cell Death
	Xie, R.; Lau, S.S.; Monks, T.J.
	2008-03-01
Source Publication	Γ-H2AX Formation is not Coupled to Elevations in Intracellular Ca2+, and Hyperactivation of PARP does not Facilitate AIF Translocation During ROS-induced Cell Death
Pages	1140.4-1140.4
Publication Place	Bethesda, Maryland, United States
Publisher	The FASEB Journal
Abstract	2,3,5-tris(Glutathion-S-yl)hydroquinone (TGHQ) is a redox-active metabolite of hydroquinone, and causes non-apoptotic cell death in renal proximal tubule epithelial cells (HK-2) via the generation of reactive oxygen species (ROS). TGHQ induced ROS generation and DNA strand breaks leads to the overactivation of poly(ADP-ribose) polymerase-1 (PARP-1), the rapid depletion of nicotinamide adenine dinucleotide (NAD+), and the appearance of γ-H2AX foci. Inhibition of PARP-1 completely blocked TGHQ-mediated poly(ADP-ribosyl)ation (PAR), NAD+ consumption, and the consequent necrotic cell death. Moreover, although Ca2+ chelation inhibited PAR and significantly abrogated cell death, NAD+ depletion was only delayed and not prevented. Despite their ability to inhibit cell death, neither PARP inhibition nor Ca2+ chelation altered ROS production or the initial DNA damage (γ-H2AX foci). Interestingly, PARP-1 hyperactivation was not accompanied by the translocation of apoptosis-inducing factor (AIF) from mitochondria to the nucleus, a process usually associated with PARP-dependent cell death. In conclusion, PARP activation and Ca2+ elevation are critical responses to ROS-mediated cell death, but at least in HK-2 cells γ-H2AX formation is not coupled to elevations in intracellular Ca2+, and PARP activation does not facilitate AIF translocation. (DK59491, P30 ES 06694).
Keyword	PARP-1 ROS Calcium cell death
URL	View the original
Language	英語English
The Source to Article	PB_Publication
PUB ID	46785
Document Type	Conference paper
Collection	DEPARTMENT OF BIOMEDICAL SCIENCES Faculty of Health Sciences
Corresponding Author	Monks, T.J.
Recommended Citation GB/T 7714	Xie, R.,Lau, S.S.,Monks, T.J.. Γ-H2AX Formation is not Coupled to Elevations in Intracellular Ca2+, and Hyperactivation of PARP does not Facilitate AIF Translocation During ROS-induced Cell Death[C], Bethesda, Maryland, United States:The FASEB Journal, 2008, 1140.4-1140.4.
APA	Xie, R.., Lau, S.S.., & Monks, T.J. (2008). Γ-H2AX Formation is not Coupled to Elevations in Intracellular Ca2+, and Hyperactivation of PARP does not Facilitate AIF Translocation During ROS-induced Cell Death. Γ-H2AX Formation is not Coupled to Elevations in Intracellular Ca2+, and Hyperactivation of PARP does not Facilitate AIF Translocation During ROS-induced Cell Death, 1140.4-1140.4.

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