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Understanding the mechanistic roles of environmental heavy metal stressors in regulating ferroptosis: adding new paradigms to the links with diseases
Understanding the mechanistic roles of environmental heavy metal stressors in regulating ferroptosis: adding new paradigms to the links with diseases
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Understanding the mechanistic roles of environmental heavy metal stressors in regulating ferroptosis: adding new paradigms to the links with diseases
Understanding the mechanistic roles of environmental heavy metal stressors in regulating ferroptosis: adding new paradigms to the links with diseases

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Understanding the mechanistic roles of environmental heavy metal stressors in regulating ferroptosis: adding new paradigms to the links with diseases
Understanding the mechanistic roles of environmental heavy metal stressors in regulating ferroptosis: adding new paradigms to the links with diseases
Journal Article

Understanding the mechanistic roles of environmental heavy metal stressors in regulating ferroptosis: adding new paradigms to the links with diseases

2023
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Overview
Ferroptosis is a new type of iron-dependent cell death induced by a failure of the lipid repair protein GPX4 or the Xc- antiporter, which is essential for glutathione production. Some heavy metals such as arsenic (As), cobalt (Co), cadmium (Cd), iron (Fe), magnesium (Mg), manganese (Mn), nickel (Ni), mercury (Hg) as well as zinc (Zn) are shown to induce ferroptotic cell death involving the generation of oxidative stress, mitochondrial dysfunctioning, lipid peroxidation, and several other cellular etiologies. However, selenium (Se) treatment has been shown to enhance adaptive transcription responses to protect cells from ferroptosis. Heavy metals like Cadmium exposure activated ALK4/5 signaling via Smad3 and Akt signaling which leads to cell death mechanism. Continuous exposure to a small dose of mercury can damage tissues, and methylmercury bind to sulfhydryl proteins and GSH, this elevates oxidative stress, free radical accumulation, glutathione depletion, mitochondrial damage, and inhibited the nuclear factor-κB pathway which leads to ferroptotic cell death. Animals exposed to nickel and cobalt may have increased lipid peroxidation which can induce ferroptosis. Glutathione depletion is caused by Zn intoxication and exposure to manganese. These metals are systemic toxins that have been shown adverse effects on humans. Ferroptosis has recently been related to several pathological disorders, including, Alzheimer’s disease, Parkinson’s disease, Huntington's disease, as well as cardiovascular disease, and any type of cancer. For these disorders and some heavy metal toxicity, ferroptosis suppression needs to be looked upon as a promising therapeutic choice.