Iron overload promotes Cyclin D1 expression and alters cell cycle in mouse hepatocytes

Troadec, Marie‐Bérengère; Courselaud, Brice; Détivaud, Lénaı̈ck; Haziza-Pigeon, Christelle; Leroyer, Patricia; Brissot, Pierre; Loréal, Olivier

doi:10.1016/j.jhep.2005.07.033

Cited by 42 publications

(40 citation statements)

References 32 publications

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“…It has also been reported that hepatic iron accumulation disrupted balance between hepatocyte proliferation and apoptosis in transgenic mice expressing HCV polyprotein 14 or in patients with chronic hepatitis C 17 . Furthermore, in vitro study using mouse hepatocytes revealed that iron overload promoted Cyclin D1 expression and accelerated hepatocyte 16 division 18 . In fact, it has been demonstrated that IRT significantly lowered hepatic 8-OHdG levels and reduced the incidence rate of HCC in patients with chronic hepatitis C 19 .…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of 6-month iron reduction therapy in patients with hepatitis C virus-related cirrhosis: a pilot study

et al. 2007

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Section: Discussionmentioning

confidence: 99%

Efficacy and safety of 6-month iron reduction therapy in patients with hepatitis C virus-related cirrhosis: a pilot study

et al. 2007

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“…The primary mechanism for physiological polyploidization involves a failure of cytokinesis, characterized by a modulation of insulin/AKT and E2F signaling (9,11,20). Interestingly, other factors can promote polyploidy in adults, such as regeneration following partial hepatectomy (48,71,72), fibrogenesis (5,73), and metabolic overload (18,74). Although some correlation exists between polyploidization and these stresses, little is known about the mechanisms leading to the genesis of polyploid hepatocytes and the consequences on liver parenchyma function.…”

Section: Discussionmentioning

confidence: 99%

Oxidative stress promotes pathologic polyploidization in nonalcoholic fatty liver disease

Gentric¹,

Maillet²,

Paradis³

et al. 2015

J. Clin. Invest.

213

196

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“…In haematological blood disorders, such as thalassemia, under production of β-protein chains reduces the expression of hepcidin [59]; which in turn, is needed to internalise and degrade ferroportin [60]. As a result, reactive oxygen species (ROS) are often produced as a consequence of this oxidative stress [58], where OH radicals are responsible for this DNA and cellular damage.…”

Section: Disorders Affecting Hepcidin Regulationmentioning

confidence: 99%

“…As a result, reactive oxygen species (ROS) are often produced as a consequence of this oxidative stress [58], where OH radicals are responsible for this DNA and cellular damage. Consequently, mutagenic products are produced, affecting purine and pyrimidine rings and its deoxyribose oxidation products [59]. An increase in ROS, therefore, increases DNA mutation levels, gene expression and cell proliferation; while sometimes inhibiting apoptosis [3].…”

Section: Disorders Affecting Hepcidin Regulationmentioning

confidence: 99%

“…As well as this, they suggest that the under production of hepcidin results in the increased formation of nontransferrin bound iron molecules (See 3.2.1), which, conversely, increases the toxicity and in some cases produces reactive oxygen species (ROS) -a consequence of this oxidative stress [58]. As a result of this DNA oxidation it could be thought that mutagenic products may directly affect the purine and pyrimidine rings, as well as deoxyribose oxidation products [59]. An increase in ROS, may, therefore, raise DNA mutation levels, gene expression, cell proliferation and in some cases, inhibit apoptosis [88].…”

Section: Mapk Pathwaymentioning

confidence: 99%

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The Regulation and Expression of Hepcidin in Carcinogenesis as a Result of Iron Overload Disorders: An Extended Literature Review

White¹

2015

JCPCR

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Aims of ProjectAs part of the research project, an extended literature review was undertaken to distinguish the relationship between hepcidin, the iron regulatory protein, and its role in the progression of carcinogenesis, based on regulation and expression in iron abundant cells. The review also aims to critically assess hepcidin's role in iron metabolism and the link between iron overload/ deficiency disorders, such as thalassemia, with the normal biological functioning of the immune system. Finally, the project aims to highlight the therapeutic uses of hepcidin in both anaemic and iron overload cancer states, with regards clinical evidence. Iron: An Introduction Biological importance of ironMaintaining Iron Concentration: Iron is the necessary molecule for cellular metabolism and is an imperative nonorganic substance, that plays a major role in oxygen transport, short-term oxygen storage [1], electron transfer [2], DNA synthesis and cell cycle phase transitioning [3]. CDK mRNA levels, for example, can be up-or down-regulated by these cell cycle control factors and triggered protein expression. Iron's physiological importance, however, is primarily determined by its oxidative state, where it has the ability to change between its ferrous (Fe2+) and ferric (Fe3+) form [4]. Thus, potentially making it a beneficial component for haemoglobin, cytochromes and several other enzymes. As well as this, iron's chemical state is important for the understanding of inorganic iron transport that is independent of transferrin [5].Iron's capability to accept and donate electrons also characterises this molecule as a toxic metal and is able to arise via the Fenton reaction, producing free radicals from converted hydrogen peroxide (H202). Thus, can cause significant damage to any proteins, DNA and fatty acids that occur within the given cell [6]. The maintenance of iron concentration is, therefore, imperative for normal biological functioning and biological systems have derived several transport and storage processes that work to achieve this homeostasis. Distribution of iron:The normal level of body iron predominantly occurs between 60-170 μg/dL [7]. Where approximately, 65 % is integrated into erythroid cells, 30% is stored within liver cell lines and bone marrow as ferritin and the remaining 5% is circulated to both myoglobin and transferrin [8]. Some circulating serum iron, however, produced by the liver must be either stored or used, to avoid the dysregulation of the bodies iron concentration [9]. Absorption of iron:Iron absorption primarily occurs in the duodenum and upper jejunum [10] and is based on a feedback mechanism that either increases or decreases iron absorption, in response to a deficient or overload state. Iron predominantly acquired from our diet is absorbed in one of two forms: as haem AbstractIron is an essential nutrient with limited bioavailability, which allows for the cell cycle progression of G1/S phases. When present in excess, iron poses a threat to cells and tissues, and therefore iron homeostasis h...

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Iron overload promotes Cyclin D1 expression and alters cell cycle in mouse hepatocytes

Cited by 42 publications

References 32 publications

Efficacy and safety of 6-month iron reduction therapy in patients with hepatitis C virus-related cirrhosis: a pilot study

Efficacy and safety of 6-month iron reduction therapy in patients with hepatitis C virus-related cirrhosis: a pilot study

Oxidative stress promotes pathologic polyploidization in nonalcoholic fatty liver disease

The Regulation and Expression of Hepcidin in Carcinogenesis as a Result of Iron Overload Disorders: An Extended Literature Review

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