ArticleToxicological sciences : an official journal of the Society of Toxicology2014
PARP-1 hyperactivation and reciprocal elevations in intracellular Ca2+ during ROS-induced nonapoptotic cell death.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 54 citations in OpenAlex.
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- The Role of Molecular and Cellular Aging Pathways on Age-Related Hearing Loss.International journal of molecular sciences · 2024Review
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- Targeting Mitochondrial Oxidative Stress as a Strategy to Treat Aging and Age-Related Diseases.Antioxidants (Basel, Switzerland) · 2023Review
- Pathological Mechanisms Induced by TRPM2 Ion Channels Activation in Renal Ischemia-Reperfusion Injury.Molecular biology reports · 2022Review
- Inherited Retinal Degeneration: PARP-Dependent Activation of Calpain Requires CNG Channel Activity.Biomolecules · 2022Article
- PARP-1 Inhibition Repressed Imbalance of Th17 and Treg Cells in Preterm Rats with Intrauterine Infection-Induced Acute Respiratory Distress Syndrome by Reducing the Expression Level of IL-6.Journal of healthcare engineering · 2022Article
- Activation of proline metabolism maintains ATP levels during cocaine-induced polyADP-ribosylation.Amino acids · 2021Article
- Effect of Cold Atmospheric Plasma on Epigenetic Changes, DNA Damage, and Possibilities for Its Use in Synergistic Cancer Therapy.International journal of molecular sciences · 2021Review
- The role of cGMP-signalling and calcium-signalling in photoreceptor cell death: perspectives for therapy development.Pflugers Archiv : European journal of physiology · 2021Review
- ATR prevents CaFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- β-Lapachone Selectively Kills Hepatocellular Carcinoma Cells by Targeting NQO1 to Induce Extensive DNA Damage and PARP1 Hyperactivation.Frontiers in oncology · 2021Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The generation of reactive oxygen species (ROS) has been implicated in the pathogenesis of renal ischemia/reperfusion injury, and many other pathological conditions. DNA strand breaks caused by ROS lead to the activation of poly(ADP-ribose)polymerase-1 (PARP-1), the excessive activation of which can result in cell death. We have utilized a model in which 2,3,5-tris(glutathion-S-yl)hydroquinone (TGHQ), a nephrotoxic and nephrocarcinogenic metabolite of hydroquinone, causes ROS-dependent cell death in human renal proximal tubule epithelial cells (HK-2), to further elucidate the role of PARP-1 in ROS-dependent cell death. TGHQ-induced ROS generation, DNA strand breaks, hyperactivation of PARP-1, rapid depletion of nicotinamide adenine dinucleotide (NAD), elevations in intracellular Ca(2+) concentrations, and subsequent nonapoptotic cell death in both a PARP- and Ca(2+)-dependent manner. Thus, inhibition of PARP-1 with PJ34 completely blocked TGHQ-mediated accumulation of poly(ADP-ribose) polymers and NAD consumption, and delayed HK-2 cell death. In contrast, chelation of intracellular Ca(2+) with BAPTA completely abrogated TGHQ-induced cell death. Ca(2+) chelation also attenuated PARP-1 hyperactivation. Conversely, inhibition of PARP-1 modulated TGHQ-mediated changes in Ca(2+) homeostasis. 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. Thus, pathways coupling PARP-1 hyperactivation to cell death are likely to be context-dependent, and therapeutic strategies designed to target PARP-1 need to recognize such variability. Our studies provide new insights into PARP-1-mediated nonapoptotic cell death, during which PARP-1 hyperactivation and elevations in intracellular Ca(2+) are reciprocally coupled to amplify ROS-induced nonapoptotic cell death.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.