α-Conotoxins, a group of small marine peptide toxins that target nAChRs with high potency and selectivity, are valuable pharmacological tools and potential drug leads. In this study, we reported the synthesis and physiological functions of a novel αM-superfamily conotoxin SIIID (CCGEGSSCPKYFKNNFICGCC) from a fish-hunting Conus striatus. Three SIIID isomers with different cystine connectivities were synthesized by solid-phase polypeptide synthesis and confirmed by mass spectrometry. Patch clamp experiments on HEK293 cells expressing nAChR subtypes showed that 1 μM SIIID (1-4, 2-5, 3-6) inhibited PNU-120596 and acetylcholine induced human α7 nAChR currents by 48.45%, which was higher than 5.08% of SIIID (1-5, 2-4, 3-6) and 9.57% of SIIID (1-6, 2-4, 3-5). Further study on the most active SIIID isomer showed that 10 μM SIIID inhibited PNU-120596 and acetylcholine induced human α7 nAChR currents by 76.33% but had no obvious effect on acetylcholine induced human α3β4 nAChR currents. In addition, SIIID inhibited PNU-120596 and acetylcholine induced human α7 nAChR currents with an IC value of 880.71 ± 271.91 nM, and this inhibition was reversible. Patch clamp experiments on rat DRG neurons showed that 10 μM SIIID had <15% inhibitory effects on sodium, potassium and calcium currents. Our results suggested that SIIID would be a promising neuropharmacology tool for the study of human α7 nAChR and its related diseases.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.toxicon.2022.03.002 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Undergraduate musculoskeletal ultrasound training based on current national guidelines-a prospective controlled study on transferability.
BMC Med Educ
October 2024
Rudolf Frey Learning Clinic, University Medical Centreof the, Johannes Gutenberg University Mainz, 55131, Mainz, Germany.
Introduction: Musculoskeletal ultrasound (MSUS) is integral to routine clinical diagnostics for musculoskeletal and joint disorders. This study aims to establish and validate a sonography course tailored to undergraduate medical students acquiring MSUS-specific skills at a German university.
Methods: A blended learning training concept, comprising 24 instruction sessions of 45 min each, was designed based on the current national guidelines of the German Society for Ultrasound in Medicine (DEGUM).
Unveiling the Bioprospecting Efficacy and Textile Dyeing of a Novel Endophytic Mycobial Red Pigment.
Indian J Microbiol
June 2024
Department of Molecular Microbiology, School of Biotechnology, Madurai Kamaraj University, Madurai, Tamilnadu 625021 India.
Article Synopsis
- Natural pigments are gaining popularity, with microbial pigments offering a reliable alternative; one fungal strain (FNG1) was identified for producing a red-orange pigment through molecular analysis.
- The pigment showed significant antimicrobial activity against various human pathogens, with effective suppression of cancer cells while not affecting non-cancerous cells, suggesting potential therapeutic uses.
- Further analysis indicated the pigment's high staining capability for cotton textiles, enhancing its utility in various applications without cytotoxic effects.
Targeting Group 3 Medulloblastoma by the Anti-PRUNE-1 and Anti-LSD1/KDM1A Epigenetic Molecules.
Int J Mol Sci
March 2024
Department of Molecular Medicine and Medical Biotechnological DMMBM, University Federico II of Naples, 80131 Naples, Italy.
Medulloblastoma (MB) is a highly malignant childhood brain tumor. Group 3 MB (Gr3 MB) is considered to have the most metastatic potential, and tailored therapies for Gr3 MB are currently lacking. Gr3 MB is driven by PRUNE-1 amplification or overexpression.
View Article and Find Full Text PDFIdentification of human MHC-I HPV18 E6/E7-specific CD8 + T cell epitopes and generation of an HPV18 E6/E7-expressing adenosquamous carcinoma in HLA-A2 transgenic mice.
J Biomed Sci
October 2022
Department of Pathology, The Johns Hopkins University, Baltimore, MD, USA.
Background: Human Papillomavirus type 18 (HPV18) is a high-risk HPV that is commonly associated with cervical cancer. HPV18 oncogenes E6 and E7 are associated with the malignant transformation of cells, thus the identification of human leukocyte antigen (HLA)-restricted E6/E7 peptide-specific CD8 + T cell epitopes and the creation of a HPV18 E6/E7 expressing cervicovaginal tumor in HLA-A2 transgenic mice will be significant for vaccine development.
Methods: In the below study, we characterized various human HLA class I-restricted HPV18 E6 and E7-specific CD8 + T cells mediated immune responses in HLA class I transgenic mice using DNA vaccines encoding HPV18E6 and HPV18E7.
Renal Replacement Techniques in Septic Shock.
Int J Mol Sci
September 2021
Kidney Center, Turku University Hospital and University of Turku, Building 4, AA7, Kiinanmyllynkatu 4-8, FIN-20521 Turku, Finland.
Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to an infection; it carries a risk for mortality, considerably exceeding that of a mere infection. Sepsis is the leading cause for acute kidney injury (AKI) and the requirement for renal replacement therapy (RRT) in intensive care unit (ICU) patients. Almost every second critically ill patient with sepsis will develop AKI.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!