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铁作为人类长寿的化学预防靶点。

Iron as a target of chemoprevention for longevity in humans.

机构信息

Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.

出版信息

Free Radic Res. 2011 Aug;45(8):906-17. doi: 10.3109/10715762.2011.564170. Epub 2011 May 26.


DOI:10.3109/10715762.2011.564170
PMID:21615276
Abstract

Iron is universally abundant and no life can exist without it. However, iron levels should be maintained within a narrow range. Iron deficiency causes anaemia, whereas excessive iron increases cancer risk, presumably by free radical generation. Several pathological conditions such as genetic haemochromatosis, chronic viral hepatitis B and C, conditions related to asbestos fibre exposure and ovarian endometriosis have been recognized as iron overload-associated conditions that also increase human cancer risks. Iron's carcinogenicity has been documented in animal experiments. Surprisingly, these studies have revealed that the homozygous deletion of CDKN2A/2B is a major hallmark of iron-induced carcinogenesis. Recently, the hormonal regulation of iron metabolism has been elucidated. A commonly hypothesized mechanism may be the lack of any iron disposal pathway other than for bleeding and a mechanism of iron re-uptake as catechol chelate has been discovered. Iron overload in neurons via the ferroportin block may play a role in Alzheimer's disease. Furthermore, a recent epidemiological study reported that iron reduction by phlebotomy was associated with decreased cancer risks in a general population. Given that the required amounts of iron decrease during ageing, the fine control of body iron stores would be a wise strategy for chemoprevention of several diseases.

摘要

铁在自然界中广泛存在,没有它任何生命都无法生存。然而,铁的含量应该保持在一个狭窄的范围内。缺铁会导致贫血,而过量的铁会增加癌症的风险,这可能是通过自由基的产生。一些病理状况,如遗传性血色素沉着症、慢性乙型和丙型肝炎、与石棉纤维暴露和卵巢子宫内膜异位症相关的状况,已被认为是与铁过载相关的状况,也会增加人类癌症的风险。铁的致癌性在动物实验中得到了证实。令人惊讶的是,这些研究表明,CDKN2A/2B 的纯合缺失是铁诱导致癌的主要标志。最近,铁代谢的激素调节已经阐明。一种常见的假设机制可能是除了出血之外没有其他铁处理途径,并且发现了一种铁再摄取的机制,即儿茶酚螯合物。通过铁蛋白阻断使神经元中铁过载可能在阿尔茨海默病中起作用。此外,最近的一项流行病学研究报告称,放血减少铁含量与普通人群癌症风险降低有关。鉴于衰老过程中铁的需求量减少,精细控制体内铁储存将是预防多种疾病的明智策略。

相似文献

[1]
Iron as a target of chemoprevention for longevity in humans.

Free Radic Res. 2011-5-26

[2]
Does excess iron play a role in breast carcinogenesis? An unresolved hypothesis.

Cancer Causes Control. 2007-12

[3]
Role of iron in carcinogenesis: cancer as a ferrotoxic disease.

Cancer Sci. 2009-1

[4]
Therapeutic potential of iron chelators in diseases associated with iron mismanagement.

J Pharm Pharmacol. 2006-5

[5]
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Toxicol Appl Pharmacol. 2005-1-15

[6]
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J Clin Pathol. 2010-12-20

[7]
The dose-dependent effects of chronic iron overload on the production of oxygen free radicals and vitamin E concentrations in the liver of a murine model.

Biol Res Nurs. 2007-4

[8]
[Iron overload and cancer].

Bull Acad Natl Med. 2000

[9]
Mysterious link between iron overload and CDKN2A/2B.

J Clin Biochem Nutr. 2010-12-28

[10]
Glucose abnormalities in non-alcoholic fatty liver disease and chronic hepatitis C virus infection: the role of iron overload.

Diabetes Metab Res Rev. 2009-7

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[4]
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[6]
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[7]
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[8]
A Bacterial Component to Alzheimer's-Type Dementia Seen via a Systems Biology Approach that Links Iron Dysregulation and Inflammagen Shedding to Disease.

J Alzheimers Dis. 2016-6-18

[9]
Ovarian endometriosis-associated stromal cells reveal persistently high affinity for iron.

Redox Biol. 2015-12

[10]
Potential scenarios leading to ovarian cancer arising from endometriosis.

Redox Rep. 2016-5

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