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Increased expression of the Abcg2 transporter during erythroid maturation plays a role in decreasing cellular protoporphyrin IX levels
Open accessAbstract
ABCG2/BCRP is a member of the adenosine triphosphate–binding cassette (ABC) transporter family and is expressed in intestine, kidney, and liver, where it modulates the absorption and excretion of xenobiotic compounds. ABCG2 is also expressed in hematopoietic stem cells and erythroid cells; however, little is known regarding its role in hematopoiesis. Abcg2 null mice have increased levels of protoporphyrin IX (PPIX) in erythroid cells, yet the mechanism for this remains uncertain. We have found that Abcg2 mRNA expression was up-regulated in differentiating erythroid cells, coinciding with increased expression of other erythroid-specific genes. This expression pattern was associated with significant amounts of ABCG2 protein on the membrane of mature peripheral blood erythrocytes. Erythroid cells engineered to express ABCG2 had significantly lower intracellular levels of PPIX, suggesting the modulation of PPIX level by ABCG2. This modulating activity was abrogated by treatment with a specific ABCG2 inhibitor, Ko143, implying that PPIX may be a direct substrate for the transporter. Taken together, our results demonstrate that ABCG2 plays a role in regulating PPIX levels during erythroid differentiation and suggest a potential role for ABCG2 as a genetic determinant in erythropoietic protoporphyria.
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“A subsequent study determined the effects of ABCG2 overexpression and transporter inhibition on intracellular and extracellular PpIX, providing compelling evidence that PpIX is an ABCG2 substrate [119].”
From 5-Aminolevulinic Acid as a Theranostic Agent for Tumor Fluorescence Imaging and Photodynamic Therapy (2023) · cites this paper as [119]
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Metadata
- Authors
- Zhou, S., Zong, Y., Ney, P. A., Nair, G., Stewart, C. F., & Sorrentino, B. P.
- Affiliations
- St. Jude Children's Research Hospital (US)
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2005-03-15
- Volume
- 105
- Issue
- 6
- Pages
- 2571-2576
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- PMC
- PMC4757428
- OpenAlex
- W1977748061
- Cited by
- 157
- References
- 31
- Citations by year
- 2026: 9 · 2025: 12 · 2024: 6 · 2023: 6 · 2022: 11 · 2021: 7 · 2020: 6 · 2019: 6 · 2018: 7 · 2017: 6 · 2016: 3 · 2015: 6 · 2014: 10 · 2013: 7 · 2012: 10
- FWCI
- 3.53
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL067366, R01-HL67366)
- National Cancer Institute (R01CA084214)
- Topics
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Porphyrin Metabolism and Disorders
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Keywords
- ABCG2, ABC transporters, erythroid maturation, protoporphyrin IX, erythropoiesis, Ko143, erythropoietic protoporphyria, erythrocyte membrane, hematopoiesis, gene expression regulation
- MeSH terms
- ATP Binding Cassette Transporter, Subfamily G, Member 2, Animals, Biological Transport, Cell Differentiation, Enzyme Inhibitors, Erythrocyte Membrane, Erythropoiesis, Humans, Intestinal Mucosa, Kidney, Liver, Organ Specificity, Protoporphyrins, Mice, Knockout, ATP-Binding Cassette Transporters, K562 Cells, Protoporphyria, Erythropoietic, Mice
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