Expression and regulation of ABCG2/BCRP1 by sex steroids in the Harderian gland of the Syrian hamster (Mesocricetus auratus)

Mares, L.; Vilchis, Felipe; Chávez, Bertha; Ramos, Luis

doi:10.1016/j.crvi.2019.11.003

Cited by 8 publications

(8 citation statements)

References 28 publications

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“…Human brain and lung tissues were frozen and stored at −80 °C before vessel isolation and RNA extraction, while mouse and rodent vessels and RNA were isolated from fresh tissues. Moreover, adult male mice and rats were used; gender/sex hormones may have affected ABC transporter expression [ 62 ]. Given that the limitations, as well as the sample size, selection and preparation, may have impacted the ABC transporter gene expression observed in the datasets, generalization of the findings observed in this study should be cautioned and made within the context of this particular study.…”

Section: Discussionmentioning

confidence: 99%

Differential Expression of ABC Transporter Genes in Brain Vessels vs. Peripheral Tissues and Vessels from Human, Mouse and Rat

et al. 2023

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Background: ATP-binding cassette (ABC) transporters comprise a superfamily of genes encoding membrane proteins with nucleotide-binding domains (NBD). These transporters, including drug efflux across the blood–brain barrier (BBB), carry a variety of substrates through plasma membranes against substrate gradients, fueled by hydrolyzing ATP. The expression patterns/enrichment of ABC transporter genes in brain microvessels compared to peripheral vessels and tissues are largely uncharacterized. Methods: In this study, the expression patterns of ABC transporter genes in brain microvessels, peripheral tissues (lung, liver and spleen) and lung vessels were investigated using RNA-seq and WesTM analyses in three species: human, mouse and rat. Results: The study demonstrated that ABC drug efflux transporter genes (including ABCB1, ABCG2, ABCC4 and ABCC5) were highly expressed in isolated brain microvessels in all three species studied; the expression of ABCB1, ABCG2, ABCC1, ABCC4 and ABCC5 was generally higher in rodent brain microvessels compared to those of humans. In contrast, ABCC2 and ABCC3 expression was low in brain microvessels, but high in rodent liver and lung vessels. Overall, most ABC transporters (with the exception of drug efflux transporters) were enriched in peripheral tissues compared to brain microvessels in humans, while in rodent species, additional ABC transporters were found to be enriched in brain microvessels. Conclusions: This study furthers the understanding of species similarities and differences in the expression patterns of ABC transporter genes; this is important for translational studies in drug development. In particular, CNS drug delivery and toxicity may vary among species depending on their unique profiles of ABC transporter expression in brain microvessels and BBB.

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Section: Discussionmentioning

confidence: 99%

Differential Expression of ABC Transporter Genes in Brain Vessels vs. Peripheral Tissues and Vessels from Human, Mouse and Rat

et al. 2023

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“…Studies on the expression analysis of BCRP have shown sex-specific expression in some tissues (Table 2 ). The expression of Bcrp gene in the Harderian gland is higher in females when compared to male hamsters [ 76 ]. The expression of Bcrp gene through the human gastrointestinal tract is similar between males and females [ 40 ].…”

Section: Regulation Of Abc Drug Transporters By Sex Hormonesmentioning

confidence: 99%

“…In the human breast cancer cell line MCF-7, the treatment with DHT downregulated Bcrp gene expression levels [ 16 ]. In rodents, gonadectomy of male hamsters increased Bcrp gene expression in the Harderian gland [ 76 ]. Also, gonadectomy in male mice did not exert any effect on BCRP expression in the kidneys but downregulated Bcrp expression in the liver of male mice.…”

Section: Regulation Of Abc Drug Transporters By Sex Hormonesmentioning

confidence: 99%

Regulation of ABC transporters by sex steroids may explain differences in drug resistance between sexes

et al. 2023

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Drug efficacy is dependent on the pharmacokinetics and pharmacodynamics of therapeutic agents. Tight junctions, detoxification enzymes, and drug transporters, due to their localization on epithelial barriers, modulate the absorption, distribution, and the elimination of a drug. The epithelial barriers which control the pharmacokinetic processes are sex steroid hormone targets, and in this way, sex hormones may also control the drug transport across these barriers. Thus, sex steroids contribute to sex differences in drug resistance and have a relevant impact on the sex-related efficacy of many therapeutic drugs. As a consequence, for the further development and optimization of therapeutic strategies, the sex of the individuals must be taken into consideration. Here, we gather and discuss the evidence about the regulation of ATP-binding cassette transporters by sex steroids, and we also describe the signaling pathways by which sex steroids modulate ATP-binding cassette transporters expression, with a focus in the most important ATP-binding cassette transporters involved in multidrug resistance.

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“…ABCG2 plays a pivotal role in extruding exogenous and endogenous substrates and drugs (Ando et al, 2007;Chen YL et al, 2016;Halwachs et al, 2016;Gewin et al, 2019;Mares et al, 2019;Orlando et al, 2019;Traxl et al, 2019), which is related to many multidrug resistant cancer cell lines, including acute lymphoblastic leukemia (ALL), retinal progenitors, hepatic metastases, gastric carcinoma, fibrosarcoma, nonsmall cell lung cancer, glioblastoma and myeloma (Natarajan et al, 2012;Olarte Carrillo et al, 2017;Abdel Gaber et al, 2018;Reustle et al, 2018;Zhang et al, 2018). ABCG2 locates in the plasma membrane of the cell and expresses in normal tissues like placenta, prostate, kidney, blood-brain barrier, liver, ovary, small intestine, and seminal vesicle (Jackson et al, 2018), which is responsible for regulating the intracellular levels of hormones, lipids, ion and intracellular organelles such as mitochondrion (Ding et al, 2019), lysosome (Chapuy et al, 2008), endoplasmic reticulum (Kashiwayama et al, 2009), Golgi apparatus (Tsuchida et al, 2008).…”

Section: Abcg2mentioning

confidence: 99%

Clinically-Relevant ABC Transporter for Anti-Cancer Drug Resistance

et al. 2021

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Multiple drug resistance (MDR), referring to the resistance of cancer cells to a broad spectrum of structurally and mechanistically unrelated drugs across membranes, severely impairs the response to chemotherapy and leads to chemotherapy failure. Overexpression of ATP binding cassette (ABC) transporters is a major contributing factor resulting in MDR, which can recognize and mediate the efflux of diverse drugs from cancer cells, thereby decreasing intracellular drug concentration. Therefore, modulators of ABC transporter could be used in combination with standard chemotherapeutic anticancer drugs to augment the therapeutic efficacy. This review summarizes the recent advances of important cancer-related ABC transporters, focusing on their physiological functions, structures, and the development of new compounds as ABC transporter inhibitors.

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Expression and regulation of ABCG2/BCRP1 by sex steroids in the Harderian gland of the Syrian hamster (Mesocricetus auratus)

Cited by 8 publications

References 28 publications

Differential Expression of ABC Transporter Genes in Brain Vessels vs. Peripheral Tissues and Vessels from Human, Mouse and Rat

Differential Expression of ABC Transporter Genes in Brain Vessels vs. Peripheral Tissues and Vessels from Human, Mouse and Rat

Regulation of ABC transporters by sex steroids may explain differences in drug resistance between sexes

Clinically-Relevant ABC Transporter for Anti-Cancer Drug Resistance

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