scholarly journals Implication of Dietary Iron-Chelating Bioactive Compounds in Molecular Mechanisms of Oxidative Stress-Induced Cell Ageing

Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 491
Author(s):  
Alexandra Barbouti ◽  
Nefeli Lagopati ◽  
Dimitris Veroutis ◽  
Vlasios Goulas ◽  
Konstantinos Evangelou ◽  
...  
Keyword(s):  
Free Radical ◽  
Molecular Mechanisms ◽  
Cellular Systems ◽  
Free Radical Theory ◽  
Radical Theory ◽  
Cellular Protection ◽  
Lipofuscin Accumulation ◽  
Labile Iron Pool ◽  
Labile Iron ◽  
Iron Pool

One of the prevailing perceptions regarding the ageing of cells and organisms is the intracellular gradual accumulation of oxidatively damaged macromolecules, leading to the decline of cell and organ function (free radical theory of ageing). This chemically undefined material known as “lipofuscin,” “ceroid,” or “age pigment” is mainly formed through unregulated and nonspecific oxidative modifications of cellular macromolecules that are induced by highly reactive free radicals. A necessary precondition for reactive free radical generation and lipofuscin formation is the intracellular availability of ferrous iron (Fe2+) (“labile iron”), catalyzing the conversion of weak oxidants such as peroxides, to extremely reactive ones like hydroxyl (HO•) or alcoxyl (RO•) radicals. If the oxidized materials remain unrepaired for extended periods of time, they can be further oxidized to generate ultimate over-oxidized products that are unable to be repaired, degraded, or exocytosed by the relevant cellular systems. Additionally, over-oxidized materials might inactivate cellular protection and repair mechanisms, thus allowing for futile cycles of increasingly rapid lipofuscin accumulation. In this review paper, we present evidence that the modulation of the labile iron pool distribution by nutritional or pharmacological means represents a hitherto unappreciated target for hampering lipofuscin accumulation and cellular ageing.

Endogenous Labile Iron Pool-Mediated Free Radical Generation for Cancer Chemodynamic Therapy

2020 ◽  
Vol 142 (36) ◽  
pp. 15320-15330 ◽  
Author(s):  
Lisen Lin ◽  
Sheng Wang ◽  
Hongzhang Deng ◽  
Weijing Yang ◽  
Lang Rao ◽  
...  
Keyword(s):  
Free Radical ◽  
Free Radical Generation ◽  
Labile Iron Pool ◽  
Radical Generation ◽  
Labile Iron ◽  
Iron Pool

scholarly journals Cytoplasmic labile iron accumulates in aging stem cells perturbing a key rheostat for identity control

2021 ◽  
Author(s):  
Yun-Ruei Kao ◽  
Jiahao Chen ◽  
Rajni Kumari ◽  
Madhuri Tatiparthy ◽  
Yuhong Ma ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Division ◽  
Adult Stem Cells ◽  
Iron Homeostasis ◽  
Molecular Mechanisms ◽  
Labile Iron Pool ◽  
Wide Range ◽  
Labile Iron ◽  
Iron Pool

Bone marrow resident and rarely dividing haematopoietic stem cells (HSC) harbour an extensive self-renewal capacity to sustain life-long blood formation; albeit their function declines during ageing. Various molecular mechanisms confer stem cell identity, ensure long-term maintenance and are known to be deregulated in aged stem cells. How these programs are coordinated, particularly during cell division, and what triggers their ageing-associated dysfunction has been unknown. Here, we demonstrate that HSC, containing the lowest amount of cytoplasmic chelatable iron (labile iron pool) among hematopoietic cells, activate a limited iron response during mitosis. Engagement of this iron homeostasis pathway elicits mobilization and β-oxidation of arachidonic acid and enhances stem cell-defining transcriptional programs governed by histone acetyl transferase Tip60/KAT5. We further find an age-associated expansion of the labile iron pool, along with loss of Tip60/KAT5-dependent gene regulation to contribute to the functional decline of ageing HSC, which can be mitigated by iron chelation. Together, our work reveals cytoplasmic redox active iron as a novel rheostat in adult stem cells; it demonstrates a role for the intracellular labile iron pool in coordinating a cascade of molecular events which reinforces HSC identity during cell division and to drive stem cell ageing when perturbed. As loss of iron homeostasis is commonly observed in the elderly, we anticipate these findings to trigger further studies into understanding and therapeutic mitigation of labile iron pool-dependent stem cell dysfunction in a wide range of degenerative and malignant pathologies.

scholarly journals Analysis of yggX and gshA Mutants Provides Insights into the Labile Iron Pool in Salmonella enterica

2008 ◽  
Vol 190 (23) ◽  
pp. 7608-7613 ◽  
Author(s):  
Michael P. Thorgersen ◽  
Diana M. Downs
Keyword(s):  
Salmonella Enterica ◽  
Iron Chelator ◽  
Fenton Chemistry ◽  
Labile Iron Pool ◽  
Growth Defects ◽  
Labile Iron ◽  
Iron Pool ◽  
Mutant Phenotypes ◽  
Permeable Iron ◽  
Iron Chelator Deferoxamine

ABSTRACT Strains of Salmonella enterica lacking YggX and the cellular reductant glutathione exhibit defects similar to those resulting from iron deficiency and oxidative stress. Mutant strains are sensitive to hydrogen peroxide and superoxide, deregulate the expression of the Fur-regulated gene entB, and fail to grow on succinate medium. Suppression of some yggX gshA mutant phenotypes by the cell-permeable iron chelator deferoxamine allowed the conclusion that increased levels of cellular Fenton chemistry played a role in the growth defects. The data presented are consistent with a scenario in which glutathione acts as a physiological chelator of the labile iron pool and in which YggX acts upstream of the labile iron pool by preventing superoxide toxicity.

scholarly journals Effects of Caloric Restriction on Cardiac Oxidative Stress and Mitochondrial Bioenergetics: Potential Role of Cardiac Sirtuins

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Ken Shinmura
Keyword(s):  
Oxidative Stress ◽  
Free Radical ◽  
Oxidative Damage ◽  
Caloric Restriction ◽  
Functional Decline ◽  
Cellular Damage ◽  
Free Radical Theory ◽  
Radical Theory ◽  
Stress Theory

The biology of aging has not been fully clarified, but the free radical theory of aging is one of the strongest aging theories proposed to date. The free radical theory has been expanded to the oxidative stress theory, in which mitochondria play a central role in the development of the aging process because of their critical roles in bioenergetics, oxidant production, and regulation of cell death. A decline in cardiac mitochondrial function associated with the accumulation of oxidative damage might be responsible, at least in part, for the decline in cardiac performance with age. In contrast, lifelong caloric restriction can attenuate functional decline with age, delay the onset of morbidity, and extend lifespan in various species. The effect of caloric restriction appears to be related to a reduction in cellular damage induced by reactive oxygen species. There is increasing evidence that sirtuins play an essential role in the reduction of mitochondrial oxidative stress during caloric restriction. We speculate that cardiac sirtuins attenuate the accumulation of oxidative damage associated with age by modifying specific mitochondrial proteins posttranscriptionally. Therefore, the distinct role of each sirtuin in the heart subjected to caloric restriction should be clarified to translate sirtuin biology into clinical practice.

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