Upregulation of cellular glutathione levels in human ABCB5- and murine Abcb5-transfected cells

Kondo, Shingo; Hongama, Keita; Hanaya, Kengo; Yoshida, Ryota; Kawanobe, Takaaki; Katayama, Kazuhiro; Noguchi, Kohji; Sugimoto, Yoshikazu

doi:10.1186/s40360-015-0038-5

Cited by 5 publications

(3 citation statements)

References 33 publications

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“…ABCB5 (ATP-binding cassette, subfamily B, member 5) is a human P-glycoprotein family member shown to be highly overexpressed in cancer stem cells (CSCs) in diverse human malignancies 5–7 . ABCB5 is relevant to clinical cancer progression and therapeutic resistance in many tumor types, including breast cancer 8–11 . However, despite the established relationship between ABCB5 and breast, and other, cancers, the intrinsic molecular role of ABCB5 in breast cancer metastasis is currently unclear.…”

Section: Introductionmentioning

confidence: 99%

ABCB5‐ZEB1 Axis Promotes Invasion and Metastasis in Breast Cancer Cells

Yao

Tian

et al. 2017

oncol res

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ABCB5 belongs to the ATP-binding cassette (ABC) superfamily, which is recognized for playing a role in the failure of chemotherapy. ABCB5 has also been found to be overexpressed at the transcriptional level in a number of cancer subtypes, including breast cancer. However, the exact mechanism ABCB5 uses on cancer cell metastasis is still unclear. In the present study, we demonstrate that ABCB5 expression was increased in metastatic tissues when compared with nonmetastatic tissues. ABCB5 can significantly enhance metastasis and epithelial-mesenchymal transition (EMT), while knockdown of ABCB5 inhibited these processes. Microarray analysis indicated that ZEB1 may function as a downstream factor of ABCB5. Furthermore, the expression of ZEB1 in tissues is positively relevant to ABCB5 in breast cancer. Knocking down ZEB1 inhibits ABCB5 ectopic expression-induced migration and invasion, as well as EMT. Taken together, these results helped to realize the oncogene functions of ABCB5 in breast cancer cells and provided a new direction in treating breast cancer.

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Section: Introductionmentioning

confidence: 99%

ABCB5‐ZEB1 Axis Promotes Invasion and Metastasis in Breast Cancer Cells

Yao

Tian

et al. 2017

oncol res

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“…The physiological role of ABCB5 remains to be unraveled. However, we can speculate that once this transporter is no longer functional, there are physiological changes that affect cell metabolism and/or mutagenesis related to toxic reactive oxygen species (Kondo et al, 2015). BRAF inhibitors alone or in combination with MEK inhibitors exert immunomodulatory effects on the tumor and its microenvironment (Deken et al, 2016; Hu-Lieskovan et al, 2015).…”

Section: Resultsmentioning

confidence: 99%

Exome Sequencing of ABCB5 Identifies Recurrent Melanoma Mutations that Result in Increased Proliferative and Invasive Capacities

Sana

Madigan

Gartner

et al. 2019

Journal of Investigative Dermatology

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ABCB5 is an ABC transporter that was shown to confer low-level multidrug resistance in cancer. In this study, we show that ABCB5 was mutated in 13.75% of the 640 melanoma samples analyzed. Besides nonsense mutations, two mutation hotspots were found in the ABCB5 protein, in the drug-binding pocket and the nucleotide-binding domains. Four mutations, which are representative of the mutation pattern, were selected. ATPase assays showed that these mutations resulted in a decrease in basal ATP hydrolysis by ABCB5. To select informative melanoma cell lines, mutational profiles of the clinical samples were further analyzed. This study showed mutations in the tumor suppressor CDKN2A gene and the NRAS oncogene in 62.5% and 75%, respectively of the samples that had mutations in the ABCB5 gene. No mutation was found in the tumor suppressor PTEN gene, whereas the activating V600E mutation in the BRAF oncogene was found in 25% of the samples with a mutated ABCB5 gene. Studies in four melanoma cell lines with various genetic backgrounds showed an increase in the proliferation and migration capacity of mutant ABCB5-expressing cells, suggesting that ABCB5 plays a role in the development of melanoma as a tumor suppressor gene.

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“…This approach permits the precise monitoring of host-synthesized GSH and its degradation product Cys-Gly in H. pylori-infected cells, thereby offering a powerful complement to conventional radiolabeling assays. While radiolabeled GSH has been extensively used to detect cellular uptake of GSH [56][57][58], radiolabeling approaches can only provide a nonspecific readout of GSH metabolism based on the intracellular accumulation and/or proteome-wide incorporation of a specified radionuclide. These methods are generally unable to resolve the exact metabolites resulting from degradation of a radiolabeled precursor.…”

Section: Plos Pathogensmentioning

confidence: 99%

Isotope tracing reveals bacterial catabolism of host-derived glutathione during Helicobacter pylori infection

Baskerville¹,

Kovalyova²,

Mejías-Luque³

et al. 2023

PLoS Pathog

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Mammalian cells synthesize the antioxidant glutathione (GSH) to shield cellular biomolecules from oxidative damage. Certain bacteria, including the gastric pathogen Helicobacter pylori, can perturb host GSH homeostasis. H. pylori infection significantly decreases GSH levels in host tissues, which has been attributed to the accumulation of reactive oxygen species in infected cells. However, the precise mechanism of H. pylori-induced GSH depletion remains unknown, and tools for studying this process during infection are limited. We developed an isotope-tracing approach to quantitatively monitor host-derived GSH in H. pylori-infected cells by mass spectrometry. Using this method, we determined that H. pylori catabolizes reduced GSH from gastric cells using γ-glutamyl transpeptidase (gGT), an enzyme that hydrolyzes GSH to glutamate and cysteinylglycine (Cys-Gly). gGT is an established virulence factor with immunomodulatory properties that is required for H. pylori colonization in vivo. We found that H. pylori internalizes Cys-Gly in a gGT-dependent manner and that Cys-Gly production during H. pylori infection is coupled to the depletion of intracellular GSH from infected cells. Consistent with bacterial catabolism of host GSH, levels of oxidized GSH did not increase during H. pylori infection, and exogenous antioxidants were unable to restore the GSH content of infected cells. Altogether, our results indicate that H. pylori-induced GSH depletion proceeds via an oxidation-independent mechanism driven by the bacterial enzyme gGT, which fortifies bacterial acquisition of nutrients from the host. Additionally, our work establishes a method for tracking the metabolic fate of host-derived GSH during infection.

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Upregulation of cellular glutathione levels in human ABCB5- and murine Abcb5-transfected cells

Cited by 5 publications

References 33 publications

ABCB5‐ZEB1 Axis Promotes Invasion and Metastasis in Breast Cancer Cells

ABCB5‐ZEB1 Axis Promotes Invasion and Metastasis in Breast Cancer Cells

Exome Sequencing of ABCB5 Identifies Recurrent Melanoma Mutations that Result in Increased Proliferative and Invasive Capacities

Isotope tracing reveals bacterial catabolism of host-derived glutathione during Helicobacter pylori infection

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