ACCN3 Blocking Peptide
- Known as:
- ACCN3 Blocking Peptide
- Catalog number:
- 33r-9439
- Product Quantity:
- USD
- Category:
- -
- Supplier:
- Fitzgerald industries international
- Gene target:
- ACCN3 Blocking Peptide
Related genes to: ACCN3 Blocking Peptide
- Gene:
- ASIC3 NIH gene
- Name:
- acid sensing ion channel subunit 3
- Previous symbol:
- ACCN3
- Synonyms:
- TNaC1, DRASIC
- Chromosome:
- 7q36.1
- Locus Type:
- gene with protein product
- Date approved:
- 1999-05-04
- Date modifiied:
- 2016-10-05
Related products to: ACCN3 Blocking Peptide
Related articles to: ACCN3 Blocking Peptide
- IntroductionEpithelial-mesenchymal transition (EMT) is a key driver of tumor invasion and metastasis, which is closely associated with poor prognosis in patients with surgically resected lung cancer. Hypercapnic acidosis (HCA) is a common comorbidity in various lung diseases; however, its specific role in regulating EMT in lung cancer remains unclear. Acid-sensing ion channel (ASIC) genes have been implicated in tumor progression, but their expression patterns and prognostic value in lung cancer, as well as their involvement in HCA-mediated EMT regulation, require further investigation.MethodsThe expression levels of ASIC genes and their prognostic significance were analyzed in lung adenocarcinoma and lung squamous cell carcinoma using the Gene Expression Profiling Interactive Analysis (GEPIA) database. A549 lung cancer cells were exposed to HCA conditions (10% CO, pH 6.69 ± 0.02) for five days to induce EMT phenotypes. Cell proliferation, migration, and invasion capacities were evaluated using corresponding functional assays. The expression levels of EMT-related markers (E-cadherin and vimentin) and ASIC3 were quantified by immunohistochemical staining, western blot analysis, and reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR). Additionally, amiloride was used to inhibit ASIC3 expression to verify its regulatory role in HCA-induced EMT.ResultsBioinformatics analysis showed that overexpression of ASIC3 mRNA was significantly correlated with reduced overall survival in lung cancer patients ( < .05). In vitro experiments demonstrated that HCA exposure significantly upregulated ASIC3 expression ( < .01) and promoted EMT in A549 cells, as evidenced by downregulated E-cadherin expression and upregulated vimentin expression. Moreover, HCA significantly enhanced the migration and invasion abilities of A549 cells ( < .01). Importantly, inhibition of ASIC3 expression by amiloride reversed all these HCA-induced effects, including the alterations in EMT markers and the enhancement of cell migratory/invasive capacities.ConclusionThe HCA microenvironment induces EMT in A549 lung cancer cells through the activation of ASIC3. These findings suggest that ASIC3 may serve as a potential therapeutic target for the treatment of lung cancer, which could help improve clinical outcomes by inhibiting tumor invasion and metastasis mediated by EMT. - Source: PubMed
Publication date: 2026/03/19
Zhao LifangZhang LihongLuo ChunyanFang XingjunYuan PeihuaQu LiangchaoFu Huan - Cardiac afferent neurons have been shown to trigger overactivation of neurohormonal systems known to drive adverse cardiac remodeling following myocardial infarction (MI). Acid-sensing ion channels (ASICs) that are highly expressed in cardiac sympathetic afferents sense ischemia-induced myocardial acidosis. We hypothesized that genetic deletion of ASICs might abrogate disadvantageous remodeling after MI by disrupting afferent signaling pathways otherwise resulting in overactivation of neurohormonal responses. To test this, we induced MI in wild type (WT) and ASIC3 mice and assessed cardiac remodeling by serial echocardiography. We found that ASIC3 mice had less LV dilation relative to ischemic zone fraction, increased LV mass and wall thickness, and increased stroke volume compared to WT mice after MI. To investigate a potential role of the autonomic nervous system, we measured renal and splanchnic sympathetic nerve activity (SNA), heart rate and systolic blood pressure variability (sBPV), and hemodynamic responses to atropine and propranolol. Following MI, ASIC3 mice had lower baroreceptor-renal SNA reflex sensitivity than WT mice, associated with elevated sBPV. Our data show that ASIC3 plays an important role in cardiac remodeling after MI potentially via modulation of baroreflex sensitivity and sBPV. ASIC3 may be further investigated as a potential therapeutic target in heart failure. - Source: PubMed
Monaghan Karley MGibbons David DWard Chad CEl-Geneidy MaramKutschke William JZimmerman Kathy AMorgan Donald AStauss Harald MHarding Anne Marie SBader Michelle C MSnyder Peter MSabharwal RasnaWeiss Robert MRahmouni KamalBenson Christopher J - Protease-activated receptor 2 (PAR2) is a G protein-coupled receptor (GPCR) expressed in both the peripheral and central nervous systems. It plays a pivotal role in mediating neuroimmune interactions, particularly in the context of inflammation and pain. Upon activation by proteases, PAR2 modulates nociception through signaling cascades that influence key ion channels, including transient receptor potential (TRP) ion channels vanilloid 1 and 4 (TRPV1 and TRPV4), ankyrin 1 (TRPA1), acid-sensing ion channel 3 (ASIC3), P2X purinoceptor 3 (P2X3), Cav3.2 (T-type Ca channel), and potassium Kv7 (M-current) channels, altering their expression and function. Through this crosstalk, PAR2 contributes to heightened neuronal excitability and pain hypersensitivity in various inflammatory conditions. In this narrative review, we highlight and discuss the mechanistic and functional interplay between PAR2 and nociceptive ion channels, which might be contributing to the pathogenesis of inflammatory pain. Targeting these specific molecular interactions between PAR2 and nociceptive ion channels may offer a promising therapeutic strategy for treating inflammatory pain. - Source: PubMed
Publication date: 2026/02/12
Aburamadan HaneenLozon YosraCyril Asha CarolineParambath Anagha NelliyullaAli Najma MohamedJan Reem KaisPlevin RobinRadhakrishnan Rajan - Inflammatory mediators including polyunsaturated fatty acids (PUFAs) are known to potentiate ASIC3 by inducing changes in multiple gating features, yet the molecular basis for their interactions remains poorly defined. Using all-atom MD simulations and electrophysiology, we show that DHA accumulates around ASIC3 through loosely coordinated interactions with a membrane-facing electropositive region along the outer leaflet of TM1. In the open state, the carboxylate head group strongly binds to a critical arginine (R63) along with nearby polar residues that are necessary to slow the rate in channel desensitization rate but not to increase the pH sensitivity for channel activation. Moreover, mutating R63 disrupted effects on ASIC3 desensitization induced by PUFAs but not N-acyl amino acids (NAAAs) or lysophosphatidylcholines (LPCs). Our results provide the first detailed description of a functional PUFA binding site on ASICs, offering new insights into lipid modulation and potential strategies for developing novel therapeutics for pain and inflammation. - Source: PubMed
Publication date: 2026/01/02
Roth RebeccaBandarupalli RamyaKlipp Robert CLi JingBankston John R - Acid-sensing ion channels (ASICs) are members of the DEG/ENaC family that includes the only known peptide-gated ion channels. While ASICs are gated by protons, they are also sensitive to peptides and are modulated by the molluscan FMRFamide and other mammalian neuropeptides ending by the RFamide motif. We identified a set of synthetic short amidated hexapeptides, which not only end by the RFamide motif but also by CFamide and FCamide, as potent positive modulators of ASIC3 acid-induced activity. We focused on two of them, a RFamide peptide (FRCC‾RFamide) and a CFamide peptide (FRCRC‾Famide), demonstrating that they have similar specificity for and effects on ASIC3. The potentiating effects of the two peptides are due to a strong slow-down of desensitization, leading to an increase in the amount of current induced by acid pH (≤pH6.6), with apparent affinities ranging from 1 to 5 μM. Surprisingly, the washout kinetic of FRCC‾RFamide peptide was much slower than those of FRCRC‾Famide and other known RFamide peptides, suggesting potential differences in their mechanisms of action. Computational modeling and structure-function analysis reveal interactions of both peptides with the non-proton binding site of ASIC3 as already reported before for other RFamide peptides, but our data also suggest possible additional effects of FRCC‾RFamide involving directly or indirectly the proton binding domain. These findings expand our understanding of ASICs' modulation by peptides, identifying novel short modulators of ASIC3, including peptides with new CFamide and FCamide ending motifs, and showing differences between these peptides using their washout kinetic as a new parameter. - Source: PubMed
Publication date: 2025/12/23
Toft MaurizioMeynier MaëvaLubrano Di Scampamorte HélèneVallée CédricSalinas MiguelZhang PeijunTacco JessicaGay Anne-SophieBourinet EmmanuelLingueglia EricDeval Emmanuel