ArticleACS chemical biology2018
Multiple Mechanisms of Zinc-Mediated Inhibition for the Apoptotic Caspases-3, -6, -7, and -8.
Article in ACS chemical biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 77 citations in OpenAlex.
- Combined Effect of Gamma Radiation and Heavy Metals on Some Living Organisms.Biological trace element research · 2025Pooled it
- The Impact of Zinc on T Cell Motility and the Immunological Synapse.International journal of molecular sciences · 2026Article
- TRPM7 Deficiency Protects Against Myocardial Ischemia-Reperfusion Injury by Regulating Intracellular ZnCirculation · 2026Article
- ZIP3 is essential for the encephalitogenic function of pTh17 cells by regulating intracellular zinc levels.Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS) · 2026Article
- A metal ion mediated functional dichotomy encodes plasticity during translation quality control.Nature communications · 2025Article
- Potential mechanisms of zinc sulfate in inhibiting porcine reproductive and respiratory syndrome virus replication: attenuation of oxidative stress, inflammatory response, and apoptosis.Frontiers in veterinary science · 2025Article
- Understanding the molecular mechanism of regeneration through apoptosis-induced compensatory proliferation studies - updates and future aspects.Apoptosis : an international journal on programmed cell death · 2024Review
- Coordination chemistry suggests that independently observed benefits of metformin and ZnBiometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2024Article
- Zn2+ decoration of microtubules arrests axonal transport and displaces tau, doublecortin, and MAP2C.The Journal of cell biology · 2023Article
- The Implications of Insufficient Zinc on the Generation of Oxidative Stress Leading to Decreased Oocyte Quality.Reproductive sciences (Thousand Oaks, Calif.) · 2023Review
- Intracellular Zinc Trafficking duringInternational journal of molecular sciences · 2023Article
- Zinc: From Biological Functions to Therapeutic Potential.International journal of molecular sciences · 2023Review
- Zinc oxide nanoparticles trigger autophagy-mediated cell death through activating lysosomal TRPML1 in normal kidney cells.Toxicology reports · 2023Article
- Aluminum Chloride-Induced Reproductive Toxicity in Rats: the Protective Role of Zinc Oxide Nanoparticles.Biological trace element research · 2022Article
- Diallyl trisulfide plays an antifibrotic role by inhibiting the expression of Bcl-2 in hepatic stellate cells.Journal of biochemical and molecular toxicology · 2022Article
- Does roundup affect zinc functions in a bivalve mollusk in ex vivo exposure?Ecotoxicology (London, England) · 2022Article
- Candidates for Repurposing as Anti-Virulence Agents Based on the Structural Profile Analysis of Microbial Collagenase Inhibitors.Pharmaceutics · 2021Article
- Aberrance of Zinc Metalloenzymes-Induced Human Diseases and Its Potential Mechanisms.Nutrients · 2021Review
- Ferritinophagy is involved in the zinc oxide nanoparticles-induced ferroptosis of vascular endothelial cells.Autophagy · 2021Article
- RevisitingBiomolecules · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Zinc is emerging as a widely used and important biological regulatory signal. Cellular zinc levels are tightly regulated by a complex array of zinc importers and exporters to control processes such as apoptotic cell death. While caspase inhibition by zinc has been reported previously, the reported inhibition constants were too weak to suggest a critical biological role for zinc-mediated inhibition. In this work, we have adopted a method of assessing available zinc. This allowed assessment of accurate inhibition constants for apoptotic caspases, caspase-3, -6, -7, and -8. Each of these caspases are inhibited by zinc at intracellular levels but with widely differing inhibition constants and different zinc binding stoichiometries. Caspase-3, -6, and -8 appear to be constitutively inhibited by typical zinc levels, and this inhibition must be lifted to allow activation. The inhibition constant for caspase-7 (76 nM) is much weaker than for the other apoptotic caspases (2.6-6.9 nM) suggesting that caspase-7 is not inactivated by normal zinc concentrations but can be inhibited under conditions of zinc stress. Caspase-3, -7, and -8 were found to bind three, one, and two zincs, respectively. In each of these caspases, zinc was present in the active site, in contrast to caspase-6, which binds one zinc allosterically. The most notable new mechanism to emerge from this work is for zinc-mediated inhibition of caspase-8. Zinc binds caspase-8 directly at the active site and at a second site. Zinc binding inhibits formation of the caspase-8 dimer, the activated form of the enzyme. Together these findings suggest that zinc plays a critical role in regulation of apoptosis by direct inactivation of caspases, in a manner that is unique for each caspase.
Indexed as
Identifiers
What OpenQuestion holds
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.