The cattle tick Rhipicephalus microplus is one of the most economically damaging livestock ectoparasites, and its widespread resistance to acaricides is a considerable challenge to its control. In this scenario, the establishment of resistant cell lines is a useful approach to understand the mechanisms involved in the development of acaricide resistance, to identify drug resistance markers, and to develop new acaricides. This study describes the establishment of an ivermectin (IVM)-resistant R. microplus embryonic cell line, BME26-IVM. The resistant cells were obtained after the exposure of IVM-sensitive BME26 cells to increasing doses of IVM in a step-wise manner, starting from an initial non-toxic concentration of 0.5 μg/mL IVM, and reaching 6 μg/mL IVM after a 46-week period. BME26-IVM cell line was 4.5 times more resistant to IVM than the parental BME26 cell line (lethal concentration 50 (LC50) 15.1 ± 1.6 μg/mL and 3.35 ± 0.09 μg/mL, respectively). As an effort to determine the molecular mechanisms governing resistance, the contribution of ATP-binding cassette (ABC) transporter was investigated. Increased expression levels of ABC transporter genes were found in IVM-treated cells, and resistance to IVM was significantly reduced by co-incubation with 5 μM cyclosporine A (CsA), an ABC transporter inhibitor, suggesting the involvement of these proteins in IVM-resistance. These results are similar to those already described in IVM-resistant tick populations, and suggest that similar resistance mechanisms are involved in vitro and in vivo. They reinforce the hypothesis that ABC transporters are involved in IVM resistance and support the use of BME26-IVM as an in vitro approach to study acaricide resistance mechanisms.
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http://dx.doi.org/10.1016/j.vetpar.2014.05.042 | DOI Listing |
Naunyn Schmiedebergs Arch Pharmacol
January 2025
Solid Tumor Research Center, Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences, Urmia, Iran.
Chemotherapy remains the cornerstone of cancer treatment; however, its efficacy is frequently compromised by the development of chemoresistance. Multidrug resistance (MDR), characterized by the refractoriness of cancer cells to a wide array of chemotherapeutic agents, presents a significant barrier to achieving successful and sustained cancer remission. One critical factor contributing to this chemoresistance is the overexpression of ATP-binding cassette (ABC) transporters.
View Article and Find Full Text PDFImmunol Res
January 2025
Inflammatory Bowel Disease Clinic, Department of Gastroenterology, National Institute of Medical Sciences and Nutrition Salvador Zubirán, Vasco de Quiroga #15, Col. Belisario Domínguez Sección XVI, 14080, Mexico City, CPCDMX, Mexico.
The ABCC subfamily contains thirteen members. Nine of these transporters are called multidrug resistance proteins (MRPs). The MRPs have been associated with developing ulcerative colitis (UC).
View Article and Find Full Text PDFEMBO J
January 2025
The Hormel Institute, University of Minnesota, Austin, MN, 55912, USA.
ABCB1 is a broad-spectrum efflux pump central to cellular drug handling and multidrug resistance in humans. However, how it is able to recognize and transport a wide range of diverse substrates remains poorly understood. Here we present cryo-EM structures of lipid-embedded human ABCB1 in conformationally distinct apo-, substrate-bound, inhibitor-bound, and nucleotide-trapped states at 3.
View Article and Find Full Text PDFJ Mol Neurosci
January 2025
Department of Biophysics, School of Life Sciences, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China.
Alzheimer's disease (AD), a prevalent neurodegenerative disorder, is characterized by mitochondrial dysfunction and immune dysregulation. This study is aimed at developing a risk prediction model for AD by integrating multi-omics data and exploring the interplay between mitochondrial energy metabolism-related genes (MEMRGs) and immune cell dynamics. We integrated four GEO datasets (GSE132903, GSE29378, GSE33000, GSE5281) for differential gene expression analysis, functional enrichment, and weighted gene co-expression network analysis (WGCNA).
View Article and Find Full Text PDFSci Rep
January 2025
Departments of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH, USA.
Approaches to mitigate the severity of infections and of immune responses are still needed for the treatment of cystic fibrosis (CF) even with the success of highly effective modulator therapies. Previous studies identified reduced levels of melatonin in a CF mouse model related to circadian rhythm dysregulation. Melatonin is known to have immunomodulatory properties and it was hypothesized that treatment with melatonin would improve responses to bacterial infection in CF mice.
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