Zinc induces CDK5 activation and neuronal death through CDK5-Tyr15 phosphorylation in ischemic stroke
Open accessAbstract
CDK5 activation promotes ischemic neuronal death in stroke, with the recognized activation mechanism being calpain-dependent p35 cleavage to p25. Here we reported that CDK5-Tyr15 phosphorylation by zinc induced CDK5 activation in brain ischemic injury. CDK5 activation and CDK5-Tyr15 phosphorylation were observed in the hippocampus of the rats that had been subjected to middle cerebral artery occlusion, both of which were reversed by pretreatment with zinc chelator; while p35 cleavage and calpain activation in ischemia were not reversed. Zinc incubation resulted in CDK5-Tyr15 phosphorylation and CDK5 activation, without increasing p35 cleavage in cultured cells. Site mutation experiment confirmed that zinc-induced CDK5 activation was dependent on Tyr15 phosphorylation. Further exploration showed that Src kinase contributed to zinc-induced Tyr15 phosphorylation and CDK5 activation. Src kinase inhibition or expression of an unphosphorylable mutant Y15F-CDK5 abolished Tyr15 phosphorylation, prevented CDK5 activation and protected hippocampal neurons from ischemic insult in rats. We conclude that zinc-induced CDK5-Tyr15 phosphorylation underlies CDK5 activation and promotes ischemic neuronal death in stroke.
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Zinc can mediate CDK5-Tyr15 phosphorylation to induce activation of CDK5.
“can mediate CDK5-Tyr15 phosphorylation to induce the activation of CDK5 [145].”
From Role of Tau Protein in Neurodegenerative Diseases and Development of Its Targeted Drugs: A Literature Review (2024) · cites this paper as [145]
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- Authors
- Tuo, Q.-Z., Liuyang, Z.-Y., Lei, P., Yan, X., Shentu, Y.-P., Liang, J.-W., Zhou, H., Pei, L., Xiong, Y., Hou, T.-Y., Zhou, X.-W., Wang, Q., Wang, J.-Z., Wang, X.-C., & Liu, R.
- Affiliations
- Sichuan University (CN)
- Huazhong University of Science and Technology (CN)
- Corresponding author
- Liu, Rong
- ORCID
- Venue
- Cell Death & Disease
- Published
- 2018-08-29
- Volume
- 9
- Issue
- 9
- Pages
- 870-870
- ISSN
- 2041-4889 (ISSN-L)
- PMC
- PMC6115431
- OpenAlex
- W2889261590
- Cited by
- 44
- References
- 45
- Citations by year
- 2026: 6 · 2025: 4 · 2024: 5 · 2023: 4 · 2022: 9 · 2021: 6 · 2020: 6 · 2019: 4
- FWCI
- 2.21
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Cell Death and Disease (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Minerva Access (University of Melbourne) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- National Natural Science Foundation of China (81471304, 81571078)
- Natural Science Foundation of Hubei Province (2017CFA065)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Calpain Protease Function and Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Neuroscience › Neurology › Neurological Disorders and Treatments
- Keywords
- zinc, cyclin-dependent kinase 5, ischemic stroke, neuronal cell death, Src kinase, calpain, zinc chelators, hippocampal neurons, middle cerebral artery occlusion, neuroprotection
- MeSH terms
- Animals, Calpain, Brain Ischemia, Hippocampus, Male, Mice, Inbred C57BL, Neurons, Phosphorylation, Zinc, Cell Death, Rats, Sprague-Dawley, src-Family Kinases, Infarction, Middle Cerebral Artery, Stroke, Cyclin-Dependent Kinase 5, Mice, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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