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Zinc Is a Potent Inhibitor of the Apoptotic Protease, Caspase-3
Open accessAbstract
The prevention of apoptosis by Zn2+ has generally been attributed to its inhibition of an endonuclease acting in the late phase of apoptosis. In this study we investigated the effect of Zn2+ on an earlier event in the apoptotic process, the proteolysis of the "death substrate" poly(ADP-ribose) polymerase (PARP). Pretreatment of intact Molt4 leukemia cells with micromolar concentrations of Zn2+ caused an inhibition of PARP proteolysis induced by the chemotherapeutic agent etoposide. Using a cell-free system consisting of purified bovine PARP as a substrate and an apoptotic extract or recombinant caspase-3 as the PARP protease, Zn2+ inhibited PARP proteolysis in the low micromolar range. To rule out an effect of Zn2+ on PARP, a protein with two zinc finger domains, we used recombinant caspase-3 and a chromogenic tetrapeptide substrate containing the caspase-3 cleavage site. In this system, Zn2+ inhibited caspase-3 with an IC50 of 0.1 microM. These results identify caspase-3 as a novel target of Zn2+ inhibition in apoptosis and suggest a regulatory role for Zn2+ in modulating the upstream apoptotic machinery.
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Citations
Cited by
The Essential Toxin: Impact of Zinc on Human Health
Plum, L. M., Rink, L., & Haase, H. (2010) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph7041342 · Cited by 1,577
Mitochondrial Release of Caspase-2 and -9 during the Apoptotic Process
Susin, S. A., Lorenzo, H. K., Zamzami, N., Marzo, I., Brenner, C., Larochette, N., Prévost, M.-C., Alzari, P. M., & Kroemer, G. (1999) · The Journal of Experimental Medicine · doi:10.1084/jem.189.2.381 · Cited by 710
The Role of Oxidative Stress and Hypoxia in Pancreatic Beta-Cell Dysfunction in Diabetes Mellitus
Gerber, P. A., & Rutter, G. A. (2017) · Antioxidants & Redox Signaling · doi:10.1089/ars.2016.6755 · Cited by 654
Critical Role of Zinc as Either an Antioxidant or a Prooxidant in Cellular Systems
Lee, S. R. (2018) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2018/9156285 · Cited by 458
Induction of Neuronal Apoptosis by Thiol Oxidation: Putative Role of Intracellular Zinc Release
Aizenman, E., Stout, A. K., Hartnett, K. A., Dineley, K. E., McLaughlin, B., & Reynolds, I. J. (2000) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2000.0751878.x · Cited by 375
Metadata
- Authors
- Perry, D. K., Smyth, M. J., Stennicke, H. R., Salvesen, G. S., Duriez, P., Poirier, G. G., & Hannun, Y. A.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1997-07
- Volume
- 272
- Issue
- 30
- Pages
- 18530-18533
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2124684134
- Cited by
- 494
- References
- 0
- FWCI
- 9.90
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- The paper
- Perry, D. K., Smyth, M. J., Stennicke, H. R., Salvesen, G. S., Duriez, P., Poirier, G. G., & Hannun, Y. A. (1997). Zinc Is a Potent Inhibitor of the Apoptotic Protease, Caspase-3. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.272.30.18530
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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