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Approximately 85% of lung cancer cases are non-small-cell lung cancer (NSCLC). Chemoresistance is a leading cause of chemotherapy failure in NSCLC treatment. Transient receptor potential cation channel subfamily V, member 1 (TRPV1), a non-selective cation channel, plays multiple roles in tumorigenesis and tumor development, including tumor cell proliferation, death, and metastasis as well as the response to therapy. In this study, we found TRPV1 expression was increased in NSCLC. overexpression induced cisplatin (DDP) and fluorouracil (5-FU) resistance in A549 cells independent of its channel function. TRPV1 expression was upregulated in A549-DDP/5-FU resistant cells, and DDP/5-FU sensitivity was restored by knockdown. overexpression mediated DDP and 5-FU resistance by upregulation of drug transporter gene expression, thereby increasing drug efflux, enhancing homologous recombination (HR) DNA repair pathway to alleviate apoptosis and activating IL-8 signaling to promote cell survival. These findings demonstrate an essential role of TRPV1 in chemoresistance in NSCLC and implicate TRPV1 as a potential chemotherapeutic target.
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http://dx.doi.org/10.3389/fonc.2022.773654 | DOI Listing |
Neuron
December 2024
State Key Laboratory of Membrane Biology, Tsinghua-Peking Center for Life Sciences, Beijing Frontier Research Center of Biological Structure, Tsinghua University, Beijing 100084, China; School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, China; IDG/McGovern Institute for Brain Research, Tsinghua University, Beijing 100084, China. Electronic address:
PIEZO1 is a mechanically activated cation channel that undergoes force-induced activation and inactivation. However, its distinct structural states remain undefined. Here, we employed an open-prone PIEZO1-S2472E mutant to capture an intermediate open structure.
View Article and Find Full Text PDFInt J Biol Macromol
December 2024
Key Laboratory of Food Processing and Quality Control, College of Food Science and Technology, Nanjing Agricultural University, Nanjing 210000, PR China. Electronic address:
Transport proteins are essential for bacterial resistance to antibiotics and toxins, but their mechanisms remain poorly understood in Bacillus subtilis. In the present study, overexpression of yoeA enhanced resistance to various antibiotics, with its expression induced by these antibiotics, especially penicillin and plipastatin. The ΔyoeA strain exhibited significant growth inhibition at 100 μg/mL of plipastatin, while as high as 10,000 μg/mL of iturin/surfactin are required to achieve comparable inhibition, suggesting a higher sensitivity of ΔyoeA to plipastatin.
View Article and Find Full Text PDFAm J Physiol Cell Physiol
December 2024
Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA, USA.
Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic disorder leading to end-stage renal disease. ADPKD arises from mutations in the and genes, which encode polycystin 1 (PC1) and polycystin 2 (PC2), respectively. PC2 is a non-selective cation channel, and disease-linked mutations disrupt normal cellular processes, including signaling and fluid secretion.
View Article and Find Full Text PDFACS Nano
December 2024
Materials Science Division, Physical and Life Sciences Directorate, Lawrence Livermore National Laboratory, Livermore, California 94550, United States.
Biological organisms engineer peptide sequences to fold into membrane pore proteins capable of performing a wide variety of transport functions. Synthetic de novo-designed membrane pores can mimic this approach to achieve a potentially even larger set of functions. Here we explore water, solute, and ion transport in three de novo designed β-barrel membrane channels in the 5-10 Å pore size range.
View Article and Find Full Text PDFJ Pharmacol Sci
January 2025
Department of Animal Radiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan; Department of Veterinary Pharmacology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan; Food and Animal Systemics, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan. Electronic address:
We investigated whether an anti-inflammatory lipid metabolite named 5,6-DiHETE reduces vascular permeability by inhibiting TRPV4 channels in vivo. In wild-type (WT) mice, histamine-induced dye extravasation was reduced by pre-administration of 5,6-DiHETE. In TRPV4-deficient mice, extravasation and histamine-induced edema were already reduced, and 5,6-DiHETE had no additional effect.
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