Origin, Function, and Fate of Metallothionein in Human Blood

Rahman, Mohammad Tariqur; Haque, Nazmul; Kasim, Noor Hayaty Abu; Ley, Marc De

doi:10.1007/112_2017_1

Cited by 30 publications

(19 citation statements)

References 131 publications

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“…In this study, hepatic Cd increased until 16 weeks and then began to decrease. These observations support a model of Cd homeostasis where hepatic Cd is released into the blood where it is taken up and terminally stored in the kidney 33 . Alternatively, the metal may be excreted into the bile and reabsorbed into the circulation via the gut 34 .…”

Section: Discussionsupporting

confidence: 82%

Cadmium and High-Fat Diet Disrupt Renal, Cardiac and Hepatic Essential Metals

Young

Yan

et al. 2019

Sci Rep

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Exposure to the environmental toxicant cadmium (Cd) contributes to the development of obesity-associated diseases. Obesity is a risk factor for a spectrum of unhealthy conditions including systemic metabolic dyshomeostasis. In the present study, the effects of whole-life exposure to environmentally-relevant concentrations of Cd on systemic essential metal distribution in adult mice fed a high-fat diet (HFD) were examined. For these studies, male and female mice were exposed to Cd-containing drinking water for >2 weeks before breeding. Pregnant mice and dams with offspring were exposed to Cd-containing drinking water. After weaning, offspring were continuously exposed to the same Cd concentration as their parents, and divided into HFD and normal (low) fat diet (LFD) groups. At 10 and 24 weeks, mice were sacrificed and blood, liver, kidney and heart harvested for metal analyses. There were significant concentration dependent increases in Cd levels in offspring with kidney > liver > heart. Sex significantly affected Cd levels in kidney and liver, with female animals accumulating more metal than males. Mice fed the HFD showed > 2-fold increase in Cd levels in the three organs compared to similarly treated LFD mice. Cadmium significantly affected essential metals levels in blood, kidney and liver. Additionally, HFD affected essential metal levels in these three organs. These findings suggest that Cd interacts with HFD to affect essential metal homeostasis, a phenomenon that may contribute to the underlying mechanism responsible for the development of obesity-associated pathologies.

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Section: Discussionsupporting

confidence: 82%

Cadmium and High-Fat Diet Disrupt Renal, Cardiac and Hepatic Essential Metals

Young

Yan

et al. 2019

Sci Rep

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“…This property makes Zn 2+ a stable ion in a biological medium and an ideal metal cofactor for reactions that require a redox-stable ion such as proteolysis and the hydration of carbon dioxide. Metallothioneins-a cysteine-rich low molecular weight group of proteins-act as reservoir of the intracellular concentration of free Zn 2+ [35][36][37]. Hence, Zn 2+ can serve as intracellular second messenger and may trigger apoptosis or a decrease in protein synthesis at elevated concentrations [38][39][40].…”

Section: Zinc In Host Immune Mechanismsmentioning

confidence: 99%

Can Zn Be a Critical Element in COVID-19 Treatment?

Rahman

Idid

2020

Biol Trace Elem Res

Self Cite

138

129

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The current COVID-19 pandemic caused by SARS-CoV-2 has prompted investigators worldwide to search for an effective antiviral treatment. A number of anti-viral drugs such as ribavirin, remdesivir, lopinavir/ritonavir, antibiotics such as azithromycin and doxycycline, and anti-parasite such as ivermectin have been recommended for COVID-19 treatment. In addition, sufficient pre-clinical rationale and evidence have been presented to use chloroquine for the treatment of COVID-19. Furthermore, Zn has the ability to enhance innate and adaptive immunity in the course of a viral infection. Besides, Zn supplement can favour COVID-19 treatment using those suggested and/or recommended drugs. Again, the effectiveness of Zn can be enhanced by using chloroquine as an ionophore while Zn inside the infected cell can stop SARS-CoV-2 replication. Given those benefits, this perspective paper describes how and why Zn could be given due consideration as a complement to the prescribed treatment of COVID-19.

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“…Peroxisomal catalase, SODs, glutathione peroxidase, and ascorbate peroxidase are antioxidant enzymes that remove O 2 ⨪, H 2 O 2 , and peroxides in cell districts, acting as highly efficient antioxidant systems that protect cellular components by variable extent. The enzymes act in concert with other proteins as peroxiredoxins [ 40 – 43 ], thioredoxins (Trx) [ 44 ], glutaredoxins (Grx) [ 45 ], and metallothionein [ 46 – 48 ] and with low molecular weight, nonenzymatic antioxidants as ascorbate, glutathione [ 45 , 49 ], tocopherol, carotenoid, and melatonin [ 50 – 53 ]. The oxidative signal is essentially reversed by two potent antioxidant systems the Trx/Trx reductase and Grx/Grx reductase, which reduce disulfides to free thiol groups at the expense of NADPH depletion.…”

Section: Ros Homeostasismentioning

confidence: 99%

Targeting Oxidatively Induced DNA Damage Response in Cancer: Opportunities for Novel Cancer Therapies

Davalli

Marverti

Lauriola

et al. 2018

Oxidative Medicine and Cellular Longevity

104

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Cancer is a death cause in economically developed countries that results growing also in developing countries. Improved outcome through targeted interventions faces the scarce selectivity of the therapies and the development of resistance to them that compromise the therapeutic effects. Genomic instability is a typical cancer hallmark due to DNA damage by genetic mutations, reactive oxygen and nitrogen species, ionizing radiation, and chemotherapeutic agents. DNA lesions can induce and/or support various diseases, including cancer. The DNA damage response (DDR) is a crucial signaling-transduction network that promotes cell cycle arrest or cell death to repair DNA lesions. DDR dysregulation favors tumor growth as downregulated or defective DDR generates genomic instability, while upregulated DDR may confer treatment resistance. Redox homeostasis deeply and capillary affects DDR as ROS activate/inhibit proteins and enzymes integral to DDR both in healthy and cancer cells, although by different routes. DDR regulation through modulating ROS homeostasis is under investigation as anticancer opportunity, also in combination with other treatments since ROS affect DDR differently in the patients during cancer development and treatment. Here, we highlight ROS-sensitive proteins whose regulation in oxidatively induced DDR might allow for selective strategies against cancer that are better tailored to the patients.

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Origin, Function, and Fate of Metallothionein in Human Blood

Cited by 30 publications

References 131 publications

Cadmium and High-Fat Diet Disrupt Renal, Cardiac and Hepatic Essential Metals

Cadmium and High-Fat Diet Disrupt Renal, Cardiac and Hepatic Essential Metals

Can Zn Be a Critical Element in COVID-19 Treatment?

Targeting Oxidatively Induced DNA Damage Response in Cancer: Opportunities for Novel Cancer Therapies

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