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.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2882908PMC
http://dx.doi.org/10.1186/1465-9921-11-60DOI Listing

Publication Analysis

Top Keywords

mrp1 protein
16
mrp1 snps
16
mrp1
12
fev1 level
12
multidrug resistance-associated
8
resistance-associated protein-1
8
protein-1 mrp1
8
protein levels
8
severity copd
8
inflammatory markers
8

Similar Publications

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.

View Article and Find Full Text PDF

Combating cisplatin-resistant lung cancer using a coiled-coil lipopeptides modified membrane fused drug delivery system.

J Control Release

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 PDF

LncRNA HOTAIR regulates the expression of MRP1 gene through the mir-6807-5p/Egr1 axis to affect the multidrug resistance of lung cancer cells.

Gene

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 PDF

The efflux pump ABCC1/MRP1 constitutively restricts PROTAC sensitivity in cancer cells.

Cell 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 PDF
Article Synopsis
  • The study aimed to explore how asiatic acid (AA) affects the drug resistance in human leukemia cells (K562/ADR) resistant to adriamycin (ADR).
  • AA was found to reduce the resistance of these cells and enhance the effectiveness of ADR, as shown by various assays including CCK-8 and flow cytometry.
  • The results indicated that AA down-regulates the expression of certain proteins related to drug resistance, suggesting a potential mechanism for reversing resistance in these cancer cells.
View Article and Find Full Text PDF

Want 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!