Up-regulation and Increased Activity of KV3.4 Channels and Their Accessory Subunit MinK-Related Peptide 2 Induced by Amyloid Peptide Are Involved in Apoptotic Neuronal Death
Abstract
The aim of the present study was to investigate whether K(V)3.4 channel subunits are involved in neuronal death induced by neurotoxic beta-amyloid peptides (Abeta). In particular, to test this hypothesis, three main questions were addressed: 1) whether the Abeta peptide can up-regulate both the transcription/translation and activity of K(V)3.4 channel subunit and its accessory subunit, MinK-related peptide 2 (MIRP2); 2) whether the increase in K(V)3.4 expression and activity can be mediated by the nuclear factor-kappaB (NF-kappaB) family of transcriptional factors; and 3) whether the specific inhibition of K(V)3.4 channel subunit reverts the Abeta peptide-induced neurodegeneration in hippocampal neurons and nerve growth factor (NGF)-differentiated PC-12 cells. We found that Abeta(1-42) treatment induced an increase in K(V)3.4 and MIRP2 transcripts and proteins, detected by reverse transcription-polymerase chain reaction and Western blot analysis, respectively, in NGF-differentiated PC-12 cells and hippocampal neurons. Patch-clamp experiments performed in whole-cell configuration revealed that the Abeta peptide caused an increase in I(A) current amplitude carried by K(V)3.4 channel subunits, as revealed by their specific blockade with blood depressing substance-I (BDS-I) in both hippocampal neurons and NGF-differentiated PC-12 cells. The inhibition of NF-kappaB nuclear translocation with the cell membrane-permeable peptide SN-50 prevented the increase in K(V)3.4 protein and transcript expression. In addition, the SN-50 peptide was able to block Abeta(1-42)-induced increase in K(V)3.4 K(+) currents and to prevent cell death caused by Abeta(1-42) exposure. Finally, BDS-I produced a similar neuroprotective effect by inhibiting the increase in K(V)3.4 expression. As a whole, our data indicate that K(V)3.4 channels could be a novel target for Alzheimer's disease pharmacological therapy.
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The antioxidant activity of limonene is crucial in preventing the increase of outward transient potassium currents, which play a critical role in triggering caspase activation and apoptotic cell death.
“In the same study, the antioxidant activity of limonene has been crucial in preventing the increase of outward transient potassium currents, which were shown to play a critical role in triggering caspase activation and apoptotic cell death (Pannaccione et al., 2007).”
From Exploring the Therapeutic Potential of Phytochemicals in Alzheimer’s Disease: Focus on Polyphenols and Monoterpenes (2022) · cites this paper as Pannaccione et al., 2007
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CALCINEURIN-MEDIATED SIGNALING IN ISCHEMIC PRECONDITIONING AND NEURONAL CELL DEATH
Shah, N. H. (2014) · D-Scholarship@Pitt (University of Pittsburgh)
- Authors
- Pannaccione, A., Boscia, F., Scorziello, A., Adornetto, A., Castaldo, P., Sirabella, R., Taglialatela, M., Renzo, G. F. D., & Annunziato, L.
- Affiliations
- University of Naples Federico II (IT)
- Istituti di Ricovero e Cura a Carattere Scientifico (IT)
- Venue
- Molecular Pharmacology
- Publisher
- Elsevier BV
- Published
- 2007-09
- Volume
- 72
- Issue
- 3
- Pages
- 665-673
- ISSN
- 0026-895X (ISSN-L)
- OpenAlex
- W2036971704
- Cited by
- 83
- References
- 38
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 2 · 2023: 1 · 2022: 8 · 2021: 4 · 2020: 5 · 2019: 6 · 2018: 4 · 2017: 5 · 2016: 2 · 2015: 2 · 2014: 3 · 2013: 6 · 2012: 3
- FWCI
- 4.23
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Archive of Doctoral Theses and Digital Collections (University of Calabria) (submittedVersion)
- Archivio Istituzionale della Ricerca - Università degli Studi del Molise (submittedVersion)
- Università Politecnica delle Marche (Università Politecnica delle Marche) (submittedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- beta-amyloid peptide, amyloid-beta 42, neuronal apoptosis, neurodegeneration, NF-κB, blood-brain barrier, hippocampal neurons, PC12 cells, Alzheimer's disease, neuroprotection, potassium currents
- MeSH terms
- Animals, Cells, Cultured, Cnidarian Venoms, Electrophysiology, Hippocampus, Neurons, Peptide Fragments, Peptides, RNA, Messenger, Sea Anemones, Up-Regulation, Amyloid beta-Peptides, NF-kappa B, PC12 Cells, Cell Death, Rats, Wistar, Apoptosis, Patch-Clamp Techniques, Rats, Shaw Potassium Channels
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