The Stem Cell Marker Bcrp/ABCG2 Enhances Hypoxic Cell Survival through Interactions with Heme

Krishnamurthy, Partha; Ross, Douglas D.; Nakanishi, Takeo; Bailey-Dell, Kim; Zhou, Sheng; Mercer, Kelly E.; Sarkadi, Balázs; Sorrentino, Brian P.; Schuetz, John D.

doi:10.1074/jbc.m313599200

Cited by 594 publications

(496 citation statements)

References 53 publications

(54 reference statements)

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“…It is well recognized that synovial infiltrating cells suffer from hypoxic stress (34). Given the notion that BCRP transcription is induced by hypoxia via the hypoxia-inducible transcription factor complex hypoxia-inducible factor 1␣ (HIF-1␣) (35), and that HIF-1␣ is particularly expressed in synovial tissue …”

Section: Discussionmentioning

confidence: 99%

Involvement of breast cancer resistance protein expression on rheumatoid arthritis synovial tissue macrophages in resistance to methotrexate and leflunomide

Heijden¹,

Oerlemans²,

Tak³

et al. 2009

Arthritis & Rheumatism

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Objective. To determine whether multidrugresistance efflux transporters are expressed on immune effector cells in synovial tissue from patients with rheumatoid arthritis (RA) and compromise the efficacy of methotrexate (MTX) and leflunomide (LEF).Methods. Synovial tissue biopsy samples obtained from RA patients before treatment and 4 months after starting treatment with MTX (n ‫؍‬ 17) or LEF (n ‫؍‬ 13) were examined by immunohistochemical staining and digital image analysis for the expression of the drug efflux transporters P-glycoprotein, multidrug resistance-associated protein 1 (MRP-1) through MRP-5, MRP-8, MRP-9, and breast cancer resistance protein (BCRP), and the relationship to clinical efficacy of MTX and LEF was assessed.Results. BCRP expression was observed in all RA synovial biopsy samples, both pretreatment and posttreatment, but not in control noninflammatory synovial tissue samples from orthopedic patients. BCRP expression was found both in the intimal lining layer and on macrophages and endothelial cells in the synovial sublining. Total numbers of macrophages in RA patients decreased upon treatment; in biopsy samples with persistently high macrophage counts, 2-fold higher BCRP expression was observed. Furthermore, median BCRP expression was significantly increased (3-fold) in nonresponders to disease-modifying antirheumatic drugs (DMARDs) compared with responders to DMARDs (P ‫؍‬ 0.048). Low expression of MRP-1 was found on synovial macrophages, along with moderate expression in T cell areas of synovial biopsy specimens from one-third of the RA patients.Conclusion. These findings show that the drug resistance-related proteins BCRP and MRP-1 are expressed on inflammatory cells in RA synovial tissue. Since MTX is a substrate for both BCRP and MRP-1, and LEF is a high-affinity substrate for BCRP, these transporters may contribute to reduced therapeutic efficacy of these DMARDs.

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Section: Discussionmentioning

confidence: 99%

Involvement of breast cancer resistance protein expression on rheumatoid arthritis synovial tissue macrophages in resistance to methotrexate and leflunomide

Heijden¹,

Oerlemans²,

Tak³

et al. 2009

Arthritis & Rheumatism

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“…Evidence from hematopoietic stem cells supports the notion that ABCG2 expression promotes cell survival. Krishnamurthy et al (2004) have shown that the expression of ABCG2 can be upregulated by the hypoxia-inducible factor 1a . Increased ABCG2 expression, in turn, facilitates the survival of bone marrow SP cells under hypoxic challenge.…”

Section: Resident Cscs Sca1 1 /Cd31 2 Cardiac Sp Cellsmentioning

confidence: 99%

Migration of Resident Cardiac Stem Cells in Myocardial Infarction

Liang

Phillips

2012

The Anatomical Record

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Ischemic heart disease is a major cause of morbidity and mortality worldwide. Stem cell-based therapy, which aims to restore cardiac structure and function by regeneration of functional myocardium, has recently been proposed as a novel alternative treatment modality. Resident cardiac stem cells (CSCs) in adult hearts are a key cell type under investigation. CSCs have been shown to be able to repair damaged myocardium and improve myocardial function in both human and animal studies. This approach relies not only on the proliferation of the CSCs, but also upon their migration to the site of injury within the heart. Here, we briefly review reported CSC populations and discuss signaling factors and pathways required for the migration of CSCs. Anat Rec, 296:184-191, 2013. V C 2012 Wiley Periodicals, Inc.

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“…Apart from being induced by chemotherapeutic drugs, ABCB1 expression and upregulation of its activity have been observed in primary rat hepatocyte culture by EGF [86]. Also, ABCB1 expression actively protects cells against cell death and ABCG2 defends against natural heme metabolites [70,[87][88][89][90][91]. By transporting a variety of exogenous and endogenous compounds out of cells, they are able to reduce the body load of potentially harmful substances.…”

Section: Abc Transportersmentioning

confidence: 99%