Implication of ABC transporters in non-proliferative diseases

Grigoreva, Tatyana A.; Sagaidak, Aleksandra; Novikova, Daria; Трибулович, В. Г.

doi:10.1016/j.ejphar.2022.175327

Cited by 13 publications

(7 citation statements)

References 180 publications

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“…For the MDR characteristic in malignant neoplasms and many other diseases, ABC transporters plays important role, and influences severely the chemotherapy effects [ 37 , 38 ]. The multi-drug resistance gene MDR1 and its encoded P-glycoprotein (P-gp) were considered to be the most noteworthy mechanisms of MDR [ 39 , 40 ].…”

Section: Discussionmentioning

confidence: 99%

Involvement and targeted intervention of benzo(a)pyrene-regulated apoptosis related proteome modification and muti-drug resistance in hepatocellular carcinoma

et al. 2023

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During the development of hepatocellular carcinoma (HCC), the mutual adaptation and interaction of HCC cells and the microenvironment play an important role. Benzo(a)pyrene (B[a]P) is a common environmental pollutant, which can induce the initiation of various malignant tumors, including HCC. However, the effects of B[a]P exposure on progression of HCC and the potential mechanisms remains largely uninvestigated. Here we found that, after the long-term exposure of HCC cells to low dose of B[a]P, it activated glucose-regulated protein 75 (GRP75), which then induced a modification of apoptosis-related proteome. Among them, we identified the X-linked inhibitor of apoptosis protein (XIAP) as a key downstream factor. XIAP further blocked the caspase cascade activation and promoted the acquisition of the anti-apoptosis abilities, ultimately leading to multi-drug resistance (MDR) in HCC. Furthermore, the abovementioned effects were markedly attenuated when we inhibited GRP75 by using 3,4-dihydroxycinnamic acid (caffeic acid, CaA). Collectively, our present study revealed the effects of B[a]P exposure on the progression of HCC, and identified GRP75 was a meaningful factor involved in.

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Section: Discussionmentioning

confidence: 99%

Involvement and targeted intervention of benzo(a)pyrene-regulated apoptosis related proteome modification and muti-drug resistance in hepatocellular carcinoma

et al. 2023

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“…The ABC transporters pathway enriched by C1orf64 refers to a family of ATP-binding cassette (ABC) transport proteins that are responsible for transporting compounds both inside and outside the cell. Enrichment in this pathway may suggest that abnormal transport of metabolites within cells is related to the occurrence and development of asthma [20,21] . The cell cycle is an important stage in the cell life cycle, including cell proliferation and differentiation, which is essential for maintaining normal physiological function [22] .…”

Section: Discussionmentioning

confidence: 99%

Exploring the Molecular Mechanisms of Asthma Across Multiple Datasets

Guo

Huang

Wang

et al. 2023

Preprint

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Objective: The aim of this research was to utilize bioinformatics techniques to explore the molecular mechanisms at the gene level that contribute to asthma, with the objective of discovering new treatment strategies and potential targets for addressing the condition. Methods: The Series Matrix File data files of GSE43696 and GSE67940 were downloaded from the NCBI GEO public database, including expression profile data of 212 patients. Differential gene expression was functionally annotated using clusterProfiler to evaluate relevant functional categories with GO and KEGG. A gene co-expression network was constructed using MEGENA, and feature importance was evaluated by random forest algorithm. Fluorescent quantitative PCR was employed to validate the expression of essential genes, and the variations in KEGG signaling pathways among the groups with high and low expression were examined through GSEA. Asthma targeted therapeutic drugs were predicted using The Connectivity Map. Finally, single-cell sequencing data were annotated and analyzed using the Seurat and celldex packages. Results: This study screened 267 differentially expressed genes between asthma patients and healthy controls from the GSE43696 dataset and further analyzed them using pathway analysis and multi-scale embedded gene co-expression network analysis, ultimately selecting 12 genes as the candidate gene set for random forest analysis. Based on this, five key genes were selected using random forest algorithm, and their expression was validated in the external dataset GSE67940. The expression of C1orf64 and C7orf26 genes was found to be different between the two groups of patients, and these two genes were found to be associated with immune regulatory factors, chemokines, and cell receptors. The mRNA expression levels of C1orf64 and C7orf26 were consistent with the results of the screening by PCR. Further analysis showed that C1orf64 and C7orf26 were enriched in ABC transporters, cell cycle, cell adhesion molecules, and Notch signaling pathways, and were related to other genes related to asthma. Finally, by classifying the differentially expressed genes using the Connectivity Map, potential clues were provided for finding candidate drugs for asthma treatment. Conclusion: This study combined bioinformatics methods to identify key genes and pathways for asthma. C1orf64 and C7orf26 genes may be the core genes in the pathogenesis of asthma in asthma patients compared to healthy controls, providing potential targets for asthma treatment. These results also suggest the potential application of drug prediction analysis using CMap and single-cell sequencing analysis in understanding the molecular mechanisms of asthma.

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“…The TMDs form the pathway by which drug molecules cross the membrane, switching between inward-and outward-facing conformations, while NBDs are responsible for binding ATP and utilizing its energy. ABCB1 is consistently expressed in most tissues, especially on the cell membrane of epithelial cells, and is responsible for the e ux of lipophilic organic cations, mainly xenobiotics; hence it is a signi cant participant of the body detoxication system (Grigoreva et al 2022; Mora Lagares and Novič 2022).…”

Section: Introductionmentioning

confidence: 99%

Comparative study on ABCB1-dependent efflux of anthracyclines and their metabolites: consequences for cancer resistance

Piska

Koczurkiewicz-Adamczyk

Jamrozik

et al. 2023

Preprint

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Purpose ABC transporters are transmembrane proteins involved in ATP-dependent translocation of organic compounds across cellular membranes. Among them, ABCB1 (P-glycoprotein, MDR1) transporter is one of the most important involved in cancer multi-drug resistance. It also plays a significant role in cancer resistance against anthracyclines, an anticancer group of drugs, including doxorubicin and daunorubicin. Carbonyl reductases and aldo-keto reductases metabolize anthracyclines to carbonyl-reduced, hydroxy metabolites, which have impaired cytotoxic properties. However, metabolites efflux by ABCB1 transporter is not well characterized, while it may be the mechanism responsible for the metabolites' lack of activity. Methods In this study recombinant ABCB1 ATPase transporter assay; anthracyclines accumulation assay in resistant cells overexpressing ABCB1; and molecular modeling were used to investigate anthracyclines: doxorubicin and daunorubicin and their carbonyl-reduced metabolites (doxorubicinol, daunorubicinol) susceptibility for ABCB1-dependent efflux. Results Based on the kinetics parameters of ATPase activity of ABCB1, it was found that daunorubicinol exerted an exceptionally high potential for being effluxed by the ABCB1 transporter. ABCB1 was found to significantly affect the accumulation pattern of studied chemicals in resistant cancer cells. Doxorubicin and daunorubicin accumulation was influenced by the activity of ABCB1 modulator – valspodar. Conclusions Results indicate that ABCB1 activity affects not only anthracyclines but also their metabolites. The effect of ABCB1 on metabolites may be even higher than for parent anthracyclines. Therefore crosstalk between the process of anthracyclines metabolism and metabolites efflux may be the mechanism of impairing anticancer properties of anthracyclines metabolites.

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Implication of ABC transporters in non-proliferative diseases

Cited by 13 publications

References 180 publications

Involvement and targeted intervention of benzo(a)pyrene-regulated apoptosis related proteome modification and muti-drug resistance in hepatocellular carcinoma

Involvement and targeted intervention of benzo(a)pyrene-regulated apoptosis related proteome modification and muti-drug resistance in hepatocellular carcinoma

Exploring the Molecular Mechanisms of Asthma Across Multiple Datasets

Comparative study on ABCB1-dependent efflux of anthracyclines and their metabolites: consequences for cancer resistance

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