Effect of metal ions on HIF-1alpha and Fe homeostasis in human A549 cells.

Effect of metal ions on HIF-1alpha and Fe homeostasis in human A549 cells. Research Abstract Details 

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Effect of metal ions on HIF-1alpha and Fe homeostasis in human A549 cells. Abstract Text:

Gi Soo Kang,Qin Li,Haobin Chen,Max Costa,

Several metals are carcinogenic but little is known about the mechanisms by which they cause cancer. A pathway that may contribute to metal ion induced carcinogenesis is by hypoxia signaling, which involves a disruption of cellular iron homeostasis by competition with iron transporters or iron-regulated enzymes. To examine the involvement of iron in the hypoxia signaling activity of these metal ions we investigated HIF-1alpha protein stabilization, IRP-1 activity, and ferritin protein levels in human lung carcinoma A459 cells exposed to various agents in serum- and iron-free salt-glucose medium (SGM) or in normal complete medium. We also studied the effects of excess exogenous iron on these responses induced by nickel ion exposure. Our results show the following: (1) SGM enhanced metals-induced HIF-1alpha stabilization and IRP-1 activation (e.g., nickel and cobalt ions). (2) If SGM was reconstituted with a slight excess level (25 microM of FeSO(4)) of iron, this enhancing ability was significantly decreased. (3) The effect of a high level of exogenous iron (500 microM of FeSO(4)) on metal-induced hypoxia and iron metabolism was highly dependent on the order of addition. If treatment with the Fe and metal ions was simultaneous (co-treatment), the effects of nickel ion exposure were overwhelmed, since the added Fe reversed HIF-1alpha stabilization, decreased IRP-1 activity, and increased ferritin level. Pre-treatment with iron was not able to reverse the responses caused by nickel ion exposure. These results imply that it is important to consider the available iron concentration and suitable exposure design when studying metal-induced hypoxia or metal-induced disruption of Fe homeostasis.

Effect of metal ions on HIF-1alpha and Fe homeostasis in human A549 cells. Publishing Authors By Initials

GS Kang,Q Li,H Chen,M Costa,

For similar enzymes and coenzymes: enzymes: lyases: carbon-oxygen lyases: hydro-lyases: aconitate hydratase: iron regulatory protein 1 research abstracts see: enzymes and coenzymes: enzymes: lyases: carbon-oxygen lyases: hydro-lyases: aconitate hydratase: iron regulatory protein 1 research

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Effect of metal ions on HIF-1alpha and Fe homeostasis in human A549 cells. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Mutation research

VOLUME: 610

Page Numbers: 48-55

Journal Abbreviation: Mutat. Res.

ISSN: 0027-5107

DAY: 31

MONTH: 07

YEAR: 2006

Effect of metal ions on HIF-1alpha and Fe homeostasis in human A549 cells. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 400763

Effect of metal ions on HIF-1alpha and Fe homeostasis in human A549 cells. Keywords Mesh Terms:

KEYWORDS: Iron Regulatory Protein 1

MESH TERMS: metabolism

Chemical & Substance for Abstract: Effect of metal ions on HIF-1alpha and Fe homeostasis in human A549 cells. Information

Substance Name: Iron Regulatory Protein 1

Registry Number: EC 4.2.1.3

Grant and Affiliation Information for Effect of metal ions on HIF-1alpha and Fe homeostasis in human A549 cells.

AFFILIATION: Department of Environmental Medicine, NYU School of Medicine, 550 First Avenue, New York, NY 10016, USA.

Country: Netherlands

AGENCY: United States NIEHS

GRANT: T32-ES07324

ACRONYM: ES

MEDLINETA: Mutat Res

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