ArticleThe Biochemical journal2015
Efficient entry of cell-penetrating peptide nona-arginine into adherent cells involves a transient increase in intracellular calcium.
Article in The Biochemical journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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
27 citing papers in PubMed.
- Membrane-Traversing Peptides: Mechanistic Landscapes, Assays, and Applications.Chemical reviews · 2026Review
- Deciphering the Influence of Side Chains of Short Cationic Hydrophobic Peptides on Macroscopic and Molecular Properties of Mixed Lipid Bilayers.The Journal of membrane biology · 2026Article
- Development of a Sensory Neuron-Integrated Skin Spheroid Model for the Evaluation of Neuropeptide-Based Topical Delivery Systems.ACS biomaterials science & engineering · 2025Article
- Multi-Functional Polymer Nanoparticles with Enhanced Adipocyte Uptake and Adipocytolytic Efficacy.Macromolecular bioscience · 2024Article
- A molecular dynamics study of cell-penetrating peptide transportan-10 (TP10): Binding, folding and insertion to transmembrane state in zwitterionic membrane.Biochimica et biophysica acta. Biomembranes · 2024Article
- Choosing an Optimal Solvent Is Crucial for Obtaining Cell-Penetrating Peptide Nanoparticles with Desired Properties and High Activity in Nucleic Acid Delivery.Pharmaceutics · 2023Article
- A hemifused complex is the hub in a network of pathways to membrane fusion.Biophysical journal · 2023Article
- Assessment of the safety of the cationic arginine-rich peptides (CARPs) poly-arginine-18 (R18 and R18D) inBiochemistry and biophysics reports · 2022Article
- Divalent Metal Ions Boost Effect of Nucleic Acids Delivered by Cell-Penetrating Peptides.Cells · 2022Article
- Bio-Membrane Internalization Mechanisms of Arginine-Rich Cell-Penetrating Peptides in Various Species.Membranes · 2022Article
- PepFect14 Signaling and Transfection.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Article
- Delivery of the VIVIT Peptide to Human Glioma Cells to Interfere with Calcineurin-NFAT Signaling.Molecules (Basel, Switzerland) · 2021Article
- Mitochondrial Targeting Domain Homologs Induce Necrotic Cell Death Via Mitochondrial and Endoplasmic Reticulum Disruption.Journal of microbiology and biotechnology · 2021Article
- Targeting Treg cells with GITR activation alleviates resistance to immunotherapy in murine glioblastomas.Nature communications · 2021Article
- A peptide for transcellular cargo delivery: Structure-function relationship and mechanism of action.Journal of controlled release : official journal of the Controlled Release Society · 2020Article
- In vitro and in vivo characterization of CPP and transferrin modified liposomes encapsulating pDNA.Nanomedicine : nanotechnology, biology, and medicine · 2020Article
- In Vitro Assays: Friends or Foes of Cell-Penetrating Peptides.International journal of molecular sciences · 2020Review
- Cell-Penetrating Peptides Enhance the Activity of Human Fibroblast Growth Factor 2 by Prolonging the Retention Time: A New Vision for Drug-Delivery Systems.International journal of molecular sciences · 2020Article
- Human Antibodies to VP4 Inhibit Replication of Enteroviruses Across Subgenotypes and Serotypes, and Enhance Host Innate Immunity.Frontiers in microbiology · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
Abstract
Understanding the mechanism of entry of cationic peptides such as nona-arginine (R9) into cells remains an important challenge to their use as efficient drug-delivery vehicles. At nanomolar to low micromolar R9 concentrations and at physiological temperature, peptide entry involves endocytosis. In contrast, at a concentration ≥10 μM, R9 induces a very effective non-endocytic entry pathway specific for cationic peptides. We found that a similar entry pathway is induced at 1-2 μM concentrations of R9 if peptide application is accompanied by a rapid temperature drop to 15°C. Both at physiological and at sub-physiological temperatures, this entry mechanism was inhibited by depletion of the intracellular ATP pool. Intriguingly, we found that R9 at 10-20 μM and 37°C induces repetitive spikes in intracellular Ca(2+) concentration. This Ca(2+) signalling correlated with the efficiency of the peptide entry. Pre-loading cells with the Ca(2+) chelator BAPTA (1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid) inhibited both Ca(2+) spikes and peptide entry, suggesting that an increase in intracellular Ca(2+) precedes and is required for peptide entry. One of the hallmarks of Ca(2+) signalling is a transient cell-surface exposure of phosphatidylserine (PS), a lipid normally residing only in the inner leaflet of the plasma membrane. Blocking the accessible PS with the PS-binding domain of lactadherin strongly inhibited non-endocytic R9 entry, suggesting the importance of PS externalization in this process. To conclude, we uncovered a novel mechanistic link between calcium signalling and entry of cationic peptides. This finding will enhance our understanding of the properties of plasma membrane and guide development of future drug-delivery vehicles.
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.