J Biol Chem. 2004 Nov 10 [Epub ahead of print] Related Articles, Links  

 
Fluctuations of intracellular iron modulate elastin production.

Bunda S, Kaviani N, Hinek A.

Division of Cardiovascular Research, The Hospital for Sick Children, Toronto,
Ontario M5G 1X8.

Production of insoluble elastin, the major component of elastic fibers, can be
modulated by numerous intrinsic and exogenous factors. Because patients with
hemolytic disorders characterized with fluctuations in iron concentration
demonstrate defective elastic fibers we speculated that iron might also
modulate elastogenesis. In the present report we demonstrate that treatment of
cultured human skin fibroblasts with low concentration of iron 2-20 microM
(ferric ammonium citrate) induced a significant increase in the synthesis of
tropoelastin and deposition of insoluble elastin. Northern blot and real time
RT-PCR analysis revealed that treatment with 20 ?M iron led to ~3-fold increase
in elastin mRNA levels. Since treatment with an intracellular iron chelator,
desferrioxamine, caused a significant decrease in elastin mRNA level and
consequent inhibition of elastin deposition, we conclude that iron facilitates
elastin gene expression. Our experimental evidence also demonstrate the
existence of an opposite effect, in which higher, but not cytotoxic
concentrations of iron (100-400 microM), induced the production of
intracellular reactive oxygen species that coincided with a significant
decrease in elastin message stability, and the disappearance of iron-dependent
stimulatory effect on elastogenesis. This stimulatory elastogenic effect was
reversed, however, in cultures simultaneously treated with high iron
concentration (200 microM) and the intracellular hydroxyl radical scavenger,
dimethylthiourea. Thus, presented data, for the first time, demonstrate the
existence of two opposite iron-dependent mechanisms that may affect the steady
state of elastin message. We speculate that extreme fluctuations in
intracellular iron levels result in impaired elastic fiber production as
observed in hemolytic diseases.

PMID: 15537639 [PubMed - as supplied by publisher]

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