A Mammalian Iron ATPase Induced by Iron

Barañano, David E.; Wolosker, Herman; Bae, Byoung-Il; Barrow, Roxanne K.; Snyder, Solomon H.; Ferris, Christopher D.

doi:10.1074/jbc.275.20.15166

Cited by 123 publications

(86 citation statements)

References 35 publications

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“…72 Moreover, ferritin production and biological activity of Fe-ATPase pump are potentiated by increased free iron in the intracellular pool due to enhanced HO-1 expression. 73,74 In summary, our data demonstrate that in rats, during a localized inflammation, the expression of HO-1 is rapidly and strongly induced in macrophages of the injured muscle and in liver parenchyma. IL-6 derived from inflammatory cells at the injured muscle seems to be responsible for the HO-1 induction in the liver but not in the other internal organs during the TO-induced APR.…”

Section: Expression Of Il-6 After To Administration and Its Possible mentioning

confidence: 92%

Upregulation of heme oxygenase-1 gene by turpentine oil-induced localized inflammation: involvement of interleukin-6

Tron¹,

Novosyadlyy²,

Dudás³

et al. 2005

Laboratory Investigation

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Heme oxygenase-1 (HO-1) is the inducible isoform of an enzyme family responsible for heme degradation and was suggested to be involved in the acute phase response in the liver. However, the mechanisms of the HO-1 regulation under inflammatory conditions are poorly understood. Therefore, the purpose of the current work was to study the expression of HO-1 in the liver and other organs of rats with a localized inflammation after intramuscular injection of turpentine oil (TO). Since interleukin-6 (IL-6) is known to be a principal mediator of inflammation, the levels of this cytokine were also estimated in the animal model used. HO-1 and IL-6 expression was evaluated by Northern blot, in situ hybridization, Western blot, immunohistochemistry and enzyme-linked immunosorbent assay. In the liver and injured muscle, the HO-1 mRNA levels were dramatically increased 4-6 h after TO administration. HO-1 protein levels in the liver were elevated starting from 6-12 h after the treatment. In other internal organs such as the heart, kidney and large intestine, only a slight induction of HO-1 mRNA was observed. IL-6-specific transcripts appeared only in the injured muscle and were in accordance with serum levels of IL-6. In turn, temporal expression of IL-6 in the muscle and circulatory IL-6 levels correlated well with HO-1 expression in the liver and injured muscle. In the liver of control rats HO-1 protein was detected in Kupffer cells, while in TO-injected rats also hepatocytes became strongly HO-1 positive. Conversely, in the injured muscle, HO-1 immunoreactivity was attributed only to macrophages. Our data demonstrate that during localized inflammation HO-1 expression was rapidly and strongly induced in macrophages of injured muscle and in hepatocytes, and IL-6 derived from injured muscle seems to be responsible for the HO-1 induction in the liver.

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Section: Expression Of Il-6 After To Administration and Its Possible mentioning

confidence: 92%

Upregulation of heme oxygenase-1 gene by turpentine oil-induced localized inflammation: involvement of interleukin-6

Tron¹,

Novosyadlyy²,

Dudás³

et al. 2005

Laboratory Investigation

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“…Under inflammatory conditions, HO-1 becomes the rate-limiting enzyme in the catabolism of heme into biliverdin, free Fe 2ϩ , and CO (15) (19,20) and activates an ATPase iron pump which also decreases the level of intracellular Fe 2ϩ (21,22). Expression of HO-1 has potent anti-inflammatory (23) and antithrombotic (24) effects in monocyte/macrophages as well as antiapoptotic effects in EC (25).…”

Section: E Ndothelial Cells (Ec)mentioning

confidence: 99%

“…Expression of HO-1 results in the up-regulation of ferritin (19) (data not shown) and is coupled to the activation of an ATPase iron pump (21,22). Given that ferritin and an ATPase iron pump act to reduce the level of intracellular Fe 2ϩ , we asked whether reduction of the reactive pool of cellular Fe 2ϩ would mimic the effect of HO-1.…”

Section: Iron Chelation Inhibits E-selectin Icam-1 and Vcam-1 Exprementioning

confidence: 99%

Heme Oxygenase-1 Modulates the Expression of Adhesion Molecules Associated with Endothelial Cell Activation

Soares

Seldon

Grégoire

et al. 2004

The Journal of Immunology

425

281

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Heme oxygenase-1 (HO-1) cleaves the porphyrin ring of heme into carbon monoxide, Fe2+, and biliverdin, which is then converted into bilirubin. Heme-derived Fe2+ induces the expression of the iron-sequestering protein ferritin and activates the ATPase Fe2+-secreting pump, which decrease intracellular free Fe2+ content. Based on the antioxidant effect of bilirubin and that of decreased free cellular Fe2+, we questioned whether HO-1 would modulate the expression of proinflammatory genes associated with endothelial cell (EC) activation. We tested this hypothesis specifically for the genes E-selectin (CD62), ICAM-1 (CD54), and VCAM-1 (CD106). We found that HO-1 overexpression in EC inhibited TNF-α-mediated E-selectin and VCAM-1, but not ICAM-1 expression, as tested at the RNA and protein level. Heme-driven HO-1 expression had similar effects to those of overexpressed HO-1. In addition, HO-1 inhibited the activation of NF-κB, a transcription factor required for TNF-α-mediated up-regulation of these genes in EC. Bilirubin and/or Fe2+ chelation mimicked the effects of HO-1, whereas biliverdin or carbon monoxide did not. In conclusion, HO-1 inhibits the expression of proinflammatory genes associated with EC activation via a mechanism that is associated with the inhibition of NF-κB activation. This effect of HO-1 is mediated by bilirubin and/or by a decrease of free intracellular Fe2+ but probably not by biliverdin or carbon monoxide.

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“…Ferritin avidly binds iron and interrupts the redox cycling of iron, thereby preventing iron from being useful as a catalyst for oxidant stress [81] . Subsequent studies have demonstrated that the induction of HO-1 is also coupled to the synthesis of iron-exporting proteins and hence a critical role of HO-1 in maintaining iron homeostasis in vivo has been suggested [82] . HO-2 is a 36 kDa protein that is widely distributed in tissues throughout the body, where it is constitutively expressed and not readily inducible [83] .…”

Section: Excretion Of Biliary Pigmentsmentioning

confidence: 99%

Excretion of biliary compounds during intrauterine life

Macı́as¹,

Marin²,

Serrano³

2009

WJG

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In adults, the hepatobiliary system, together with the kidney, constitute the main routes for the elimination of several endogenous and xenobiotic compounds into bile and urine, respectively. However, during intrauterine life the biliary route of excretion for cholephilic compounds, such as bile acids and biliary pigments, is very poor. Although very early in pregnancy the fetal liver produces bile acids, bilirubin and biliverdin, these compounds cannot be efficiently eliminated by the fetal hepatobiliary system, owing to the immaturity of the excretory machinery in the fetal liver. Therefore, the potentially harmful accumulation of cholephilic compounds in the fetus is prevented by their elimination across the placenta. Owing to the presence of detoxifying enzymes and specific transport systems at different locations of the placental barrier, such as the endothelial cells of chorionic vessels and trophoblast cells, this organ plays an important role in the hepatobiliary-like function during intrauterine life. The relevance of this excretory function in normal fetal physiology is evident in situations where high concentrations of biliary compounds are accumulated in the mother. This may result in oxidative stress and apoptosis, mainly in the placenta and fetal liver, which might affect normal fetal development and challenge the fate of the pregnancy. The present article reviews current knowledge of the mechanisms underlying the hepatobiliary function of the fetal-placental unit and the repercussions of several pathological conditions on this tandem.

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A Mammalian Iron ATPase Induced by Iron

Cited by 123 publications

References 35 publications

Upregulation of heme oxygenase-1 gene by turpentine oil-induced localized inflammation: involvement of interleukin-6

Upregulation of heme oxygenase-1 gene by turpentine oil-induced localized inflammation: involvement of interleukin-6

Heme Oxygenase-1 Modulates the Expression of Adhesion Molecules Associated with Endothelial Cell Activation

Excretion of biliary compounds during intrauterine life

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