Ferric iron uptake into cardiomyocytes of β-thalassemic mice is not through calcium channels
Iron-overload cardiomyopathy is a major cause of death in thalassemic patients. However, pathways of non-transferrin-bound iron (NTBI) uptake into cardiomyocytes under iron-overload conditions are still controversial. We previously demonstrated that Fe2+uptake in thalassemic cardiomyocytes is mainly...
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| Main Authors: | , , , |
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| Format: | Journal |
| Published: |
2018
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| Subjects: | |
| Online Access: | https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84871211904&origin=inward http://cmuir.cmu.ac.th/jspui/handle/6653943832/52324 |
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| Institution: | Chiang Mai University |
| Summary: | Iron-overload cardiomyopathy is a major cause of death in thalassemic patients. However, pathways of non-transferrin-bound iron (NTBI) uptake into cardiomyocytes under iron-overload conditions are still controversial. We previously demonstrated that Fe2+uptake in thalassemic cardiomyocytes is mainly mediated by T-type calcium channels (TTCCs). However, direct evidence regarding Fe3+uptake, the other form of NTBI, in thalassemic cardiomyocytes has never been investigated. Hearts from genetic-altered β-thalassemic mice and adult wild-type (WT) mice were used for cultured ventricular cardiomyocytes. Blockers for L-type calcium channel (LTCC), TTCC, transferrin receptor1 (TfR1), and divalent metal transporter1 (DMT1) were used, and quantification of cellular iron uptake was performed by the acetoxymethyl ester of calcein fluorescence assay. Cellular uptake of Fe3+under iron-overload conditions in cultured ventricular myocytes of thalassemic mice was greater than that of WT cells (P < 0.01). The iron chelator, deferoxamine, could prevent Fe3+uptake into cultured cardiomyocytes. However, blockers of TfR1, DMT1, LTCC, and TTCC could not prevent Fe3+uptake into cardiomyocytes. Our findings indicated that, unlike Fe2+, Fe3+uptake in cultured thalassemic cardiomyocytes is not mainly mediated by TfR1, DMT1, LTCC, and TTCC, suggesting that another alternative pathway could play a major role in Fe3+uptake in thalassemic cardiomyocytes. © 2013 Informa Healthcare USA, Inc. |
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