Zinc regulates reactive oxygen species generation in platelets

Lopes-Pires, Maria Elisa; Ahmed, Niaz S.; Vara, Dina S.; Gibbins, Jonathan M.; Pula, Giordano; Pugh, Nicholas

doi:10.1080/09537104.2020.1742311

Cited by 24 publications

(21 citation statements)

References 72 publications

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“…117,118 We have recently investigated the relationship between ROS generation and [Zn 2+ ] i in platelets. 110 [120][121][122][123][124][125] consistent with GpVI being the most potent stimulator of [Zn 2+ ] i responses. Platelets express both NOX1 and NOX2.…”

Section: Release Of Zn 2+ Upon Platelet Degranulationmentioning

confidence: 75%

Zinc: an endogenous and exogenous regulator of platelet function during hemostasis and thrombosis

2020

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Zinc (Zn 2+ ) is an essential micronutrient and the second most abundant trace metal in the human body. The important role that Zn 2+ plays in haemostasis is exemplified by platelet-related bleeding phenotypes coinciding with dietary Zn 2+ deficiency. These phenotypes are rectified upon Zn 2+ supplementation. Labile (unbound) Zn 2+ is present in the plasma at micromolar levels, but is also detected in atherosclerotic plaques, and released from platelet alpha granules. Therefore, it is likely that localised Zn 2+ concentrations are higher at sites of thrombosis and haemostasis. Exogenous Zn 2+ is a regulator of the haemostatic responses, with roles during coagulation and platelet activation. Extracellular Zn 2+ gains access to the platelet cytosol and induces full platelet activation at high concentrations, and potentiates platelets to activation by conventional agonists at lower concentrations. Zn 2+ -induced platelet activation is dependent on PKC and integrin α IIb β 3 , and is associated with tyrosine phosphorylation of platelet proteins. Agonist evoked platelet activation results in intracellular Zn 2+ ([Zn 2+ ] i ) fluctuations that are sensitive to the platelet redox state. Increases in [Zn 2+ ] i correlate with activation responses, including shape change, granule release, α IIb β 3 activation and phosphatidylserine exposure, consistent with a role as a second messenger. This review provides insight into the numerous demonstrated and potential roles for Zn 2+ in platelet function during thrombosis and haemostasis, highlighting its increasing acceptance as an intracellular and extracellular platelet regulatory agent.

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Section: Release Of Zn 2+ Upon Platelet Degranulationmentioning

confidence: 75%

Zinc: an endogenous and exogenous regulator of platelet function during hemostasis and thrombosis

2020

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“…In addition, low ROS concentration can promote cell proliferation, whereas excessive ROS levels cause DNA oxidative damage, consequently inducing cell death [ 105 ]. ROS levels are implicated in all blood cell lines death: platelets [ 106 , 107 ], RBCs [ 108 , 109 ], and WBCs [ 110 , 111 ].…”

Section: Discussionmentioning

confidence: 99%

Usnic Acid and Usnea barbata (L.) F.H. Wigg. Dry Extracts Promote Apoptosis and DNA Damage in Human Blood Cells through Enhancing ROS Levels

et al. 2021

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Nowadays, numerous biomedical studies performed on natural compounds and plant extracts aim to obtain highly selective pharmacological activities without unwanted toxic effects. In the big world of medicinal plants, Usnea barbata (L) F.H. Wigg (U. barbata) and usnic acid (UA) are well-known for their therapeutical properties. One of the most studied properties is their cytotoxicity on various tumor cells. This work aims to evaluate their cytotoxic potential on normal blood cells. Three dry U. barbata extracts in various solvents: ethyl acetate (UBEA), acetone (UBA), and ethanol (UBE) were prepared. From UBEA we isolated usnic acid with high purity by semipreparative chromatography. Then, UA, UBA, and UBE dissolved in 1% dimethyl sulfoxide (DMSO) and diluted in four concentrations were tested for their toxicity on human blood cells. The blood samples were collected from a healthy non-smoker donor; the obtained blood cell cultures were treated with the tested samples. After 24 h, the cytotoxic effect was analyzed through the mechanisms that can cause cell death: early and late apoptosis, caspase 3/7 activity, nuclear apoptosis, autophagy, reactive oxygen species (ROS) level and DNA damage. Generally, the cytotoxic effect was directly proportional to the increase of concentrations, usnic acid inducing the most significant response. At high concentrations, usnic acid and U. barbata extracts induced apoptosis and DNA damage in human blood cells, increasing ROS levels. Our study reveals the importance of prior natural products toxicity evaluation on normal cells to anticipate their limits and benefits as potential anticancer drugs.

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“…Zinc influences thrombocyte aggregation and coagulation ( 150 ). Recently, a functional association between zinc and ROS production in platelets was described, indicating that zinc could decrease thrombus formation in a clinical context ( 151 ). Complications of SARS-CoV2 infections also include tissue damage affecting the gastrointestinal system ( 152 ), the liver ( 153 ), heart ( 154 ), nervous system ( 155 ), kidneys ( 156 ), blood vessels ( 149 ), and the skin ( 157 ).…”

Section: Risk Groups and Symptoms Of Covid-19 And Zinc Deficiency Revmentioning

confidence: 99%

The Potential Impact of Zinc Supplementation on COVID-19 Pathogenesis

2020

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During the current corona pandemic, new therapeutic options against this viral disease are urgently desired. Due to the rapid spread and immense number of affected individuals worldwide, cost-effective, globally available, and safe options with minimal side effects and simple application are extremely warranted. This review will therefore discuss the potential of zinc as preventive and therapeutic agent alone or in combination with other strategies, as zinc meets all the above described criteria. While a variety of data on the association of the individual zinc status with viral and respiratory tract infections are available, study evidence regarding COVID-19 is so far missing but can be assumed as was indicated by others and is detailed in this perspective, focusing on re-balancing of the immune response by zinc supplementation. Especially, the role of zinc in viral-induced vascular complications has barely been discussed, so far. Interestingly, most of the risk groups described for COVID-19 are at the same time groups that were associated with zinc deficiency. As zinc is essential to preserve natural tissue barriers such as the respiratory epithelium, preventing pathogen entry, for a balanced function of the immune system and the redox system, zinc deficiency can probably be added to the factors predisposing individuals to infection and detrimental progression of COVID-19. Finally, due to its direct antiviral properties, it can be assumed that zinc administration is beneficial for most of the population, especially those with suboptimal zinc status.

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Zinc regulates reactive oxygen species generation in platelets

Abstract: Short running head: Zn 2+ regulates platelet ROS production

Cited by 24 publications

References 72 publications

Zinc: an endogenous and exogenous regulator of platelet function during hemostasis and thrombosis

Zinc: an endogenous and exogenous regulator of platelet function during hemostasis and thrombosis

Usnic Acid and Usnea barbata (L.) F.H. Wigg. Dry Extracts Promote Apoptosis and DNA Damage in Human Blood Cells through Enhancing ROS Levels

The Potential Impact of Zinc Supplementation on COVID-19 Pathogenesis

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