Abstract | BACKGROUND: METHODS: Fe(II) and Fe(III) uptake was assessed by exposing HL-1 cardiomyocytes to iron sources and quantitative real-time fluorescence imaging of cytosolic labile iron with the fluorescent iron sensor calcein while iron-induced apoptosis was quantitatively measured by flow cytometry analysis with Annexin V. The role of calcium channels as routes of iron uptake was assessed by cell pretreatment with specific blockers of LTCC and TTCC. RESULTS:
Iron entered HL-1 cardiomyocytes in a time- and dose-dependent manner and induced cardiac apoptosis via mitochondria-mediated caspase-3 dependent pathways. Blockade of LTCC but not of TTCC demonstrably inhibited the uptake of ferric but not of ferrous iron. However, neither channel blocker conferred cardiomyocytes with protection from iron-induced apoptosis. CONCLUSION: Our study implicates LTCC as major mediators of Fe(III) uptake into cardiomyocytes exposed to ferric salts but not necessarily as contributors to ensuing apoptosis. Thus, to the extent that apoptosis can be considered a biological indicator of damage, the etiopathology of cardiosiderotic damage that accompanies some forms of hemosiderosis would seem to be unrelated to LTCC or TTCC, but rather to other routes of iron ingress present in heart cells.
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Authors | Mei-pian Chen, Z Ioav Cabantchik, Shing Chan, Godfrey Chi-fung Chan, Yiu-fai Cheung |
Journal | PloS one
(PLoS One)
Vol. 9
Issue 11
Pg. e112915
( 2014)
ISSN: 1932-6203 [Electronic] United States |
PMID | 25390893
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Calcium Channel Blockers
- Calcium Channels, L-Type
- Calcium Channels, T-Type
- Ferric Compounds
- Iron
- Caspase 3
- Calcium
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Topics |
- Animals
- Apoptosis
(drug effects)
- Calcium
(metabolism)
- Calcium Channel Blockers
(pharmacology)
- Calcium Channels, L-Type
(metabolism)
- Calcium Channels, T-Type
(metabolism)
- Cardiomyopathies
(metabolism)
- Caspase 3
(metabolism)
- Cell Line
- Ferric Compounds
(pharmacology)
- Heart
(drug effects)
- Iron
(metabolism)
- Iron Overload
(metabolism)
- Mice
- Mitochondria
(drug effects, metabolism)
- Myocytes, Cardiac
(drug effects, metabolism)
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