Calcium-channel blockers do not affect iron transport mediated by divalent metal-ion transporter-1

Mackenzie, Bryan; Shawki, Ali; Ghio, Andrew J.; Stonehuerner, Jacqueline; Zhao, Lin; Ghadersohi, Saied; Garrick, Laura M.; Garrick, Michael D.

doi:10.1182/blood-2010-03-274738

Cited by 12 publications

(13 citation statements)

References 10 publications

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“…These results offer nifedipine as a means of modulating iron overload in a fashion that would be off-label use of a USA FDA-approved drug. We [33] have not been able to reproduce the stimulation of DMT1 by nifedipine and suggest that the ability of photodegraded nifedipine to serve as an iron channel [19,44,45] may account for some of their observations. Unfortunately, their statistical analysis [31] supporting the argument that the DMT1 mutation diminishes the loss of serum iron is flawed and the postulated role of DMT1 in supporting exit of iron would make DMT1 join Fpn as an iron exporter.…”

Section: Liver Contributionsmentioning

confidence: 77%

Human iron transporters

Garrick

2010

Genes Nutr

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Human iron transporters manage iron carefully because tissues need iron for critical functions, but too much iron increases the risk of reactive oxygen species. Iron acquisition occurs in the duodenum via divalent metal transporter (DMT1) and ferroportin. Iron trafficking depends largely on the transferrin cycle. Nevertheless, nondigestive tissues have a variety of other iron transporters that may render DMT1 modestly redundant, and DMT1 levels exceed those needed for the just-mentioned tasks. This review begins to consider why and also describes advances after 2008 that begin to address this challenge.

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Section: Liver Contributionsmentioning

confidence: 77%

Human iron transporters

Garrick

2010

Genes Nutr

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“…Furthermore, calcium channel blockers have been reported to mitigate iron overload by enhancing the activity of DMT1 (136). However, these data have been disputed (137). Despite the evidence from in vitro studies supporting a role for LVGCCs in iron trafficking, mice lacking Ca v 1.2 to 1.3 do not exhibit alterations in iron metabolism (138).…”

Section: Cellular Iron Metabolismmentioning

confidence: 99%

Mechanisms of Mammalian Iron Homeostasis

Pantopoulos

Porwal²,

Tartakoff³

et al. 2012

Biochemistry

476

459

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Iron is vital for almost all organisms because of its ability to donate and accept electrons with relative ease. It serves as a cofactor for many proteins and enzymes necessary for oxygen and energy metabolism, as well as for several other essential processes. Mammalian cells utilize multiple mechanisms to acquire iron. Disruption of iron homeostasis is associated with various human diseases: iron deficiency resulting from defects in the acquisition or distribution of the metal causes anemia, whereas iron surfeit resulting from excessive iron absorption or defective utilization causes abnormal tissue iron deposition, leading to oxidative damage. Mammals utilize distinct mechanisms to regulate iron homeostasis at the systemic and cellular levels. These involve the hormone hepcidin and iron regulatory proteins, which collectively ensure iron balance. This review outlines recent advances in iron regulatory pathways as well as in mechanisms underlying intracellular iron trafficking, an important but less studied area of mammalian iron homeostasis.

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“…However, the effects were attributed to nifedipine and not its photodegradation products. Conflicting results were obtained when Mackenzie, Garrick, and colleagues (84) rigorously examined nifedipine effects on DMT1 in vitro. In their study, the parent compound did not increase DMT1-mediated transport of 59 Fe or 54 Mn.…”

Section: Iron Transport Inhibitors and Stimulatorsmentioning

confidence: 99%

Pharmacology of Iron Transport

Byrne

Krishnamurthy²,

Wessling‐Resnick

2013

Annu. Rev. Pharmacol. Toxicol.

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Elucidating the molecular basis for the regulation of iron uptake, storage, and distribution is necessary to understand iron homeostasis. Pharmacological tools are emerging to identify and distinguish among different iron transport pathways. Stimulatory or inhibitory small molecules with effects on iron uptake can help characterize the mechanistic elements of iron transport and the roles of the transporters involved in these processes. In particular, iron chelators can serve as potential pharmacological tools to alleviate diseases of iron overload. This review focuses on the pharmacology of iron transport, introducing iron transport membrane proteins and known inhibitors.

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Calcium-channel blockers do not affect iron transport mediated by divalent metal-ion transporter-1

Cited by 12 publications

References 10 publications

Human iron transporters

Human iron transporters

Mechanisms of Mammalian Iron Homeostasis

Pharmacology of Iron Transport

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