Background: Multidrug resistance-associated protein-1 (MRP1) protects against oxidative stress and toxic compounds generated by cigarette smoking, which is the main risk factor for chronic obstructive pulmonary disease (COPD). We have previously shown that single nucleotide polymorphisms (SNPs) in MRP1 significantly associate with level of FEV1 in two independent population based cohorts. The aim of our study was to assess the associations of MRP1 SNPs with FEV1 level, MRP1 protein levels and inflammatory markers in bronchial biopsies and sputum of COPD patients.
Methods: Five SNPs (rs212093, rs4148382, rs504348, rs4781699, rs35621) in MRP1 were genotyped in 110 COPD patients. The effects of MRP1 SNPs were analyzed using linear regression models.
Results: One SNP, rs212093 was significantly associated with a higher FEV1 level and less airway wall inflammation. Another SNP, rs4148382 was significantly associated with a lower FEV1 level, higher number of inflammatory cells in induced sputum and with a higher MRP1 protein level in bronchial biopsies.
Conclusions: This is the first study linking MRP1 SNPs with lung function and inflammatory markers in COPD patients, suggesting a role of MRP1 SNPs in the severity of COPD in addition to their association with MRP1 protein level in bronchial biopsies.
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http://dx.doi.org/10.1186/1465-9921-11-60 | DOI Listing |
Int J Mol Sci
December 2024
Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan 50612, Republic of Korea.
Ovarian cancer (OC) is the second most common female reproductive cancer and the most lethal gynecological malignancy worldwide. Most human OCs are characterized by high rates of drug resistance and metastasis, leading to poor prognosis. Improving the outcomes of patients with relapsed and treatment-resistant OC remains a challenge.
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January 2025
State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; Haihe Laboratory of Modern Chinese Medicine, Tianjin 301617, China. Electronic address:
Drug resistance to chemotherapy in treating cancers becomes an increasingly serious challenge, which leads to treatment failure and poor patient survival. Drug-resistant cancer cells normally reduce intracellular accumulation of drugs by controlling drug uptake and promoting drug efflux, which severely limits the efficacy of chemotherapy. To overcome this problem, a membrane fused drug delivery system (MF-DDS) was constructed to treat cisplatin (DDP)-resistant lung cancer (A549-DDP) by delivering DDP via membrane fusion using a complementary coiled-coil forming peptides (CPK/CPE).
View Article and Find Full Text PDFGene
January 2025
Department of Life Science and Agroforestry, Qiqihar University, 42 Wenhua Street, Qiqihar 161006, Heilongjiang Province, China; Key Laboratory of Resistance Gene Engineering and Protection of Biodiversity in Cold Areas, Qiqihar University, 42 Wenhua Street, Qiqihar 161006, Heilongjiang Province, China. Electronic address:
Multi-drug resistance-associated protein 1 (MRP1) plays critical roles in the multi-drug resistance (MDR) of cancer cells, LncRNA HOTAIR is closely related to MDR in lung cancer, however, the effects of HOTAIR on MRP1 expression and MDR in lung cancer cells (A549/DDP) remain unknown. In this study, the effects of HOTAIR on MRP1 gene expression and MDR in A549/DDP cells were monitored. LncRNA HOTAIR was upregulated in A549/DDP cells, and overexpression of HOTAIR promoted MRP1 expression and MDR development.
View Article and Find Full Text PDFCell Chem Biol
December 2024
CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria; Center for Physiology and Pharmacology, Medical University of Vienna, 1090 Vienna, Austria. Electronic address:
Proteolysis targeting chimeras (PROTACs) are bifunctional molecules that induce selective protein degradation by linking an E3 ubiquitin ligase enzyme to a target protein. This approach allows scope for targeting "undruggable" proteins, and several PROTACs have reached the stage of clinical candidates. However, the roles of cellular transmembrane transporters in PROTAC uptake and efflux remain underexplored.
View Article and Find Full Text PDFZhongguo Shi Yan Xue Ye Xue Za Zhi
December 2024
Department of Pediatrics, Binzhou Medical University Hospital, Binzhou 256603, Shandong Province, China.
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