Differential effects on cellular iron metabolism of the physiologically relevant diatomic effector molecules, NO and CO, that bind iron.

  title={Differential effects on cellular iron metabolism of the physiologically relevant diatomic effector molecules, NO and CO, that bind iron.},
  author={Ralph N. Watts and Des R Richardson},
  journal={Biochimica et biophysica acta},
  volume={1692 1},

Carbon monoxide reversibly alters iron homeostasis and respiratory epithelial cell function.

It is concluded that CO reduces the iron content of the lung through both the metal uptake and release mechanisms, in line with certain biological effects of the gas that have been implicated in the protection of cell viability.

Nitrogen monoxide (NO)-mediated iron release from cells is linked to NO-induced glutathione efflux via multidrug resistance-associated protein 1

Data indicate the importance of GSH in NO-mediated inhibition of proliferation and active transport of NO by MRP1 overcomes diffusion that is inefficient and nontargeted, which has broad ramifications for understanding NO biology.

CO as a cellular signaling molecule.

Recent findings reveal that HO-derived CO may act as an oxygen sensor and circadian modulator of heme biosynthesis and, in lymphocytes, CO may participate in regulatory T cell function.

Nitrogen Monoxide (NO) Storage and Transport by Dinitrosyl-Dithiol-Iron Complexes: Long-lived NO That Is Trafficked by Interacting Proteins*

The generation of dinitrosyl-dithiol-iron complexes acts as a common currency for NO transport and storage by MRP1 and GST P1-1, respectively.

The role of reactive oxygen and nitrogen species in cellular iron metabolism

It is suggested that reactive oxygen and nitrogen species can significantly affect iron metabolism and their interaction with iron-regulatory proteins (IRPs) seems to be one of the essential mechanisms of influencing iron homeostasis.

Role of gas molecules in the mitochondrial transport of erythroid-specific 5-aminolevulinate synthase (ALAS2)

The role of certain gas molecules, namely oxygen (O2), nitric oxide (NO), peroxynitrite (ONOO) and carbon monoxide (CO), on ALAS2 expression and mitochondrial import was significantly inhibited by SNP, SIN-1, CO and hypoxia treatments compared to normoxia and the data suggests that theALAS2 feedback mechanism cannot be regulated by the binding of heme to the leader sequence of ALas2.

Nitric oxide and frataxin: two players contributing to maintain cellular iron homeostasis.

How NO production constitutes a key response in plant iron sensing and availability is discussed and how frataxin, a recently identified protein in plants, plays an important role in mitochondria biogenesis and in maintaining mitochondrial iron homeostasis is discussed.



Effects of nitrogen monoxide and carbon monoxide on molecular and cellular iron metabolism: mirror-image effector molecules that target iron.

Preliminary evidence suggests that, like NO, CO plays important roles in Fe metabolism, suggesting that CO has a similar effect to NO on Fe trafficking.

Examination of the mechanism of action of nitrogen monoxide on iron uptake from transferrin.

The experiments demonstrate that NO produced by the NO generator S-nitroso-N-acetylpenicillamine was slightly more effective than the Fe chelator deferoxamine at reducing iron 59 uptake from 59Fe-labeled Tf by LMTK- fibroblasts and suggest that D-G acts as a salvage metabolite to prevent the NO-mediated decrease in ATP levels and Fe uptake from Tf.

Nitrogen Monoxide (NO) and Glucose

It is demonstrated that d-Glc metabolism via the hexose monophosphate shunt resulting in the generation of GSH may be essential for NO-mediated 59Fe release, which has important implications for intracellular signaling by NO and also NO- mediated cytotoxicity of activated macrophages that is due, in part, to iron release from tumor target cells.

The effect of intracellular iron concentration and nitrogen monoxide on Nramp2 expression and non-transferrin-bound iron uptake.

The experiments show that the IRE in Nramp2 mRNA does bind the IRPs in lysates from a mouse fibroblast cell line (LMTK-), but incubation with DFO and FAC did not result in appropriate regulation of Fe uptake from [59 Fe]nitrilotriacetate or [59Fe]citrate, and demonstrate that non-Tf-bound Fe uptake was not under control of the IRP-IRE system in these cells.

The mechanism of nitrogen monoxide (NO)-mediated iron mobilization from cells. NO intercepts iron before incorporation into ferritin and indirectly mobilizes iron from ferritin in a glutathione-dependent manner.

The data suggest that NO intercepts 59Fe on route to ferritin, and indirectly facilitates removal of 59Fe from the protein, and proposes a model of glucose-dependent NO-mediated Fe mobilization.

Nitrogen monoxide activates iron regulatory protein 1 RNA-binding activity by two possible mechanisms: effect on the [4Fe-4S] cluster and iron mobilization from cells.

The results suggest that NO could activate IRP1 RNA-binding by two possible mechanisms: (1) its direct effect on the [4Fe-4S] cluster and (2) mobilization of (59)Fe from cells resulting in Fe depletion, which then increasesIRP1RNA-binding activity.

Heme oxygenase-1-derived carbon monoxide is an autocrine inhibitor of vascular smooth muscle cell growth.

It is demonstrated that serum stimulates HO-1 gene expression and CO synthesis and it is shown that CO acts in a negative feedback fashion to inhibit vascular SMC growth by regulating specific components of the cell cycle machinery.