ArticleThe Journal of biological chemistry2012
Melittin modulates keratinocyte function through P2 receptor-dependent ADAM activation.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 45 citations in OpenAlex.
- Melittin attenuates imiquimod-induced psoriatic dermatitis in mice: a role for autophagy activation via PI3K/Akt/mTOR pathway suppression.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2026Article
- Mechanoresponsive ion channels Piezo1 and TRPV4 stimulate ADAM10 and ADAM17 with differential impact on endothelial migration and proliferation.Cell communication and signaling : CCS · 2026Article
- Recent Advancement in Novel Wound Healing Therapies by Using Antimicrobial Peptides Derived from Humans and Amphibians.Current protein & peptide science · 2024Review
- Breakdown of Phospholipid Asymmetry Triggers ADAM17-Mediated Rescue Events in Cells Undergoing Apoptosis.Membranes · 2023Article
- Socio-Economic Factors Affecting Member's Satisfaction towards National Health Insurance: An Evidence from the Philippines.International journal of environmental research and public health · 2022Article
- Lysophosphatidylserine Induces MUC5AC Production via the Feedforward Regulation of the TACE-EGFR-ERK Pathway in Airway Epithelial Cells in a Receptor-Independent Manner.International journal of molecular sciences · 2022Article
- Investigations on the Wound Healing Potential of Tilapia Piscidin (TP)2-5 and TP2-6.Marine drugs · 2022Article
- Scramblases as Regulators of ProteolyticMembranes · 2022Review
- Article
- Role of ADAM10 and ADAM17 in Regulating CD137 Function.International journal of molecular sciences · 2021Article
- Polarization of ADAM17-driven EGFR signalling in electric field-guided collective migration of epidermal sheets.Journal of cellular and molecular medicine · 2020Article
- ACE2/ADAM17/TMPRSS2 Interplay May Be the Main Risk Factor for COVID-19.Frontiers in immunology · 2020Review
- ADAM10 sheddase activation is controlled by cell membrane asymmetry.Journal of molecular cell biology · 2019Article
- Antimicrobial endotoxin-neutralizing peptides promote keratinocyte migration via P2X7 receptor activation and accelerate wound healing in vivo.British journal of pharmacology · 2018Article
- Antimicrobial Peptides and Their Therapeutic Potential for Bacterial Skin Infections and Wounds.Frontiers in pharmacology · 2018Review
- TT-1, an analog of melittin, triggers apoptosis in human thyroid cancer TT cells via regulating caspase, Bcl-2 and Bax.Oncology letters · 2018Article
- Anti-hepatocarcinoma activity of TT-1, an analog of melittin, combined with interferon-α via promoting the interaction of NKG2D and MICA.Journal of Zhejiang University. Science. B · 2017Article
- Roles of extracellular nucleotides and P2 receptors in ectodomain shedding.Cellular and molecular life sciences : CMLS · 2016Review
- Synthetic antimicrobial and LPS-neutralising peptides suppress inflammatory and immune responses in skin cells and promote keratinocyte migration.Scientific reports · 2016Article
- Kinetic Defects Induced by Melittin in Model Lipid Membranes: A Solution Atomic Force Microscopy Study.The journal of physical chemistry. B · 2016Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Melittin, the major component of the bee venom, is an amphipathic, cationic peptide with a wide spectrum of biological properties that is being considered as an anti-inflammatory and anti-cancer agent. It modulates multiple cellular functions but the underlying mechanisms are not clearly understood. Here, we report that melittin activates disintegrin-like metalloproteases (ADAMs) and that downstream events likely contribute to the biological effects evoked by the peptide. Melittin stimulated the proteolysis of ADAM10 and ADAM17 substrates in human neutrophil granulocytes, endothelial cells and murine fibroblasts. In human HaCaT keratinocytes, melittin induced shedding of the adhesion molecule E-cadherin and release of TGF-α, which was accompanied by transactivation of the EGF receptor and ERK1/2 phosphorylation. This was followed by functional consequences such as increased keratinocyte proliferation and enhanced cell migration. Evidence is provided that ATP release and activation of purinergic P2 receptors are involved in melittin-induced ADAM activation. E-cadherin shedding and EGFR phosphorylation were dose-dependently reduced in the presence of ATPases or P2 receptor antagonists. The involvement of P2 receptors was underscored in experiments with HEK cells, which lack the P2X7 receptor and showed strikingly increased response to melittin stimulation after transfection with this receptor. Our study provides new insight into the mechanism of melittin function which should be of interest particularly in the context of its potential use as an anti-inflammatory or anti-cancer agent.
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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.