Dynamics of the cytosolic chelatable iron pool of K562 cells

Breuer, William; Epsztejn, Silvina; Cabantchik, Z. Ioav

doi:10.1016/0014-5793(96)00190-1

Cited by 103 publications

(56 citation statements)

References 29 publications

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“…It has been shown that cells treated with lower than 25 M iron (supplied as FAC) are able to maintain an equilibrium between LIP and iron bound to ferritin without a disturbance in cellular metabolism (45). Results of the present in vitro study demonstrate, for the first time, that treatment of normal human skin fibroblasts with such concentrations of iron can up-regulate tropoelastin synthesis and its final extracellular deposition into elastin fibers.…”

Section: Discussionmentioning

confidence: 55%

“…Confluent cultures were then treated for 72 h with or without FAC producing iron concentrations from 2 to 200 M. The low iron concentration (2 and 20 M) of iron utilized in the present study remained in the range that did not induce any disturbances in cellular metabolism when tested by other investigators (45). The high iron concentration (200 M) was comparable to concentrations used in studies of iron overload (41,46).…”

Section: Methodsmentioning

confidence: 61%

“…Previously published data (45) indicated that treatment with elevated iron concentrations (100 -200 M FAC) causes an expansion in the LIP that cannot be buffered by the sequestration capacity of cellular ferritin. The high iron concentration (100 -200 M) utilized in the present study was comparable to concentrations used in other investigations of iron overload (41,46).…”

Section: Discussionmentioning

confidence: 99%

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Fluctuations of Intracellular Iron Modulate Elastin Production

Bunda

Kaviani

Hinek

2005

Journal of Biological Chemistry

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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 M (ferric ammonium citrate) induced a significant increase in the synthesis of tropoelastin and deposition of insoluble elastin. Northern blot and realtime reverse transcription-PCR analysis revealed that treatment with 20 M iron led to an increase of ϳ3-fold in elastin mRNA levels. Because 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 demonstrates the existence of an opposite effect, in which higher, but not cytotoxic concentrations of iron (100 -400 M) 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 M) 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.Mature elastic fibers and laminae provide extensibility and elastic recoil to vascular walls and ligaments and form a connective tissue framework of lungs, elastic cartilage, and skin (1, 2). They are complex structures made of polymeric (insoluble) elastin and 12-nm microfibrils that consist of several glycoproteins, e.g. fibrillins, fibulins, and microfibril-associated glycoproteins (3-6). Elastic fiber formation (elastogenesis) is a complex process involving several intracellular and extracellular events. Cells (fibroblasts, endothelial cells, chondroblasts, or vascular smooth muscle cells) must first synthesize and secrete numerous glycoproteins to form a microfibrillar scaffold upon which tropoelastin, the precursor peptides, are properly assembled and covalently cross-linked by lysyl oxidase into a resilient polymer, insoluble elastin (7-10). Production of elastin reaches its highest levels in the third trimester of the fetal life and steadily decreases during early postnatal development (11,12). In undisturbed tissues, elastic fibers may last over the entire human lifespan (13,14).The net deposition of elastin appears to be controlled on both the transcriptional level (tropoelastin mRNA message express...

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Section: Discussionmentioning

confidence: 55%

Section: Methodsmentioning

confidence: 61%

Section: Discussionmentioning

confidence: 99%

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Fluctuations of Intracellular Iron Modulate Elastin Production

Bunda

Kaviani

Hinek

2005

Journal of Biological Chemistry

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“…The excess iron deposition is associated with fibrosis and cirrhosis [33]. Oxidative damage in K562 cells is associated with the appearance LIP after treatment with transferrin-bound iron or FAC [34]. Both ferric and ferrous ions have been reported to induce lipid peroxidation in HepG2 cells [22,23].…”

Section: Discussionmentioning

confidence: 99%

Efficacy of 1-(N-acetyl-6-aminohexyl)-3-hydroxypyridin-4-one (CM1) in treatment of iron-loaded hepatocyte cultures

Pangjit¹,

Banjerdpongchai²,

Phisalaphong³

et al. 2012

ABB

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Excessive iron is toxic to cells and organelles, where it can generate harmful reactive oxygen species (ROS) resulting in oxidative tissue damage. Liver is the major organ for iron storage and redox active iron in this tissue can cause fibrosis and cirrhosis in β-thalassemia patients. Desferrioxamine (DFO), deferiprone (DFP) and deferasirox (DFX) are clinically approved iron chelators used for the treatment of patients with iron overload, but none of these chelators are completely free of side effects. In this study we report the properties of a new iron chelator 1-(Nacetyl-6-aminohexyl)-3-hydroxypyridin-4-one (CM1). The labile iron pool (LIP) content was measured by using a calcein fluorescence technique and the lipidperoxidation products were quantified using the thiobarbituric acid reactive substances (TBARS) method. The cytotoxicity of CM1 was also examined with the (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. CM1 was demonstrated to reduce iron-induced redox damage and to decrease the levels of the intracellular iron pool in hepatocytes. CM1 is a potentially useful iron-chelating agent which has potential to ameliorate liver iron overload and ROS-induced lipid peroxidation. CM1 is currently under investigation for oral efficacy.

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“…The labile iron pool of cells constitutes a cytosolic fraction of low molecular weight (LMW) chelators bound iron or bioavailable iron, which can be characterized as iron (a) exchangeable and chelatable; (b) easily bioavailable for uptake by ferritin, heme, transferrin, or chelators; (c) metabolically and catalytically reactive for oxidant formation and likely responsible for iron toxicity; (d) possibly having regulatory properties which may affect iron responsive element-binding protein activity per se. 31,32 Recently iron status has been examined as a contributor to carcinogenesis, [33][34][35][36][37][38] and has been associated with increased risk of cancer in several epidemiological studies. 34,37,38 Factors which increase reactive oxygen species, such as smoking, inflammation, bioavailable iron, and reduced antioxidant activity may adversely affect the natural history of HPV infections by increasing the oxidant:antioxidant balance and directly influence transcriptional activity.…”

Section: Hpv and Cervical Carcinogenesismentioning

confidence: 99%

Cervical carcinogenesis: the role of co-factors and generation of reactive oxygen species

Giuliano

2003

Salud pública Méx

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ResumenDiversos co-factores de riesgo han sido asociados consistentemente con displasia cervical y cáncer invasor. Es necesario un mayor número de investigaciones que utilicen diseños de cohorte prospectivos para describir el proceso de carcinogénesis y el mecanismo biológico de cada uno de estos factores. Adicionalmente, futuras investigaciones serán necesarias para definir el papel de los anticonceptivos hormonales en la promoción de la carcinogénesis cervical. Mientras que muchas preguntas científicas interesantes permanecen sin ser respondidas, resultados de numerosos estudios epidemiológicos que se desarrollan actualmente, indican que la displasia cervical y cáncer podrán ser reducidos si la tasa de oxidantes-antioxidantes es cambiada a más de un perfil antioxidante. Además de la detección oportuna de cáncer cervical, puede lograrse una reducción de la incidencia de esta enfermedad disminuyendo el consumo de tabaco, incrementando el estatus nutricional, y utilizando métodos contraceptivos de barrera para prevenir otras infecciones de transmisión sexual. Este artículo también está disponible en: http://www.insp.mx/salud/index.html Palabras clave: cáncer cervical; co-factores de riesgo; antioxidantes; nutrición; prevención This paper is available too at: http://www.insp.mx/salud/index.html Abstract Several HPV co-factors have been proposed, some more or less consistently associated with cervical dysplasia and cancer risk. More research, using prospective cohort designs, is needed to further describe where in carcinogenesis these factors are working and to assess the biological mechanism of these factors. In addition, further research is needed to define the role of various hormonal contraceptive formulations in promoting cervical carcinogenesis. While many interesting scientific questions remain to be answered, results from the numerous epidemiological studies conducted to date indicate that cervical dysplasia and cancer may be reduced if the oxidant antioxidant ratio is shifted to more of and antioxidant profile. In addition to cervical cancer screening, a reduction in cervical cancer incidence may be accomplished by reducing tobacco use, increasing nutritional status, and utilizing barrier contraception to prevent infection with other sexually acquired infections. This paper is available too at: http:// www.insp.mx/salud/index.html

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Dynamics of the cytosolic chelatable iron pool of K562 cells

Cited by 103 publications

References 29 publications

Fluctuations of Intracellular Iron Modulate Elastin Production

Fluctuations of Intracellular Iron Modulate Elastin Production

Efficacy of 1-(N-acetyl-6-aminohexyl)-3-hydroxypyridin-4-one (CM1) in treatment of iron-loaded hepatocyte cultures

Cervical carcinogenesis: the role of co-factors and generation of reactive oxygen species

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