Advances in metal-induced oxidative stress and human disease

Zinc (Zn) is an essential component of thousands of proteins in plants, although it is toxic in excess. In this review, the dominant fluxes of Zn in the soil-root-shoot continuum are described, including Zn inputs to soils, the plant availability of soluble Zn(2+) at the root surface, and plant uptake and accumulation of Zn. Knowledge of these fluxes can inform agronomic and genetic strategies to address the widespread problem of Zn-limited crop growth. Substantial within-species genetic variation in Zn composition is being used to alleviate human dietary Zn deficiencies through biofortification. Intriguingly, a meta-analysis of data from an extensive literature survey indicates that a small proportion of the genetic variation in shoot Zn concentration can be attributed to evolutionary processes whose effects manifest above the family level. Remarkable insights into the evolutionary potential of plants to respond to elevated soil Zn have recently been made through detailed anatomical, physiological, chemical, genetic and molecular characterizations of the brassicaceous Zn hyperaccumulators Thlaspi caerulescens and Arabidopsis halleri.

Zinc in plants

The use of zinc in medicinal skin cream was mentioned in Egyptian papyri from 2000 BC (for example, the Smith Papyrus), and zinc has apparently been used fairly steadily throughout Roman and modern times (for example, as the American lotion named for its zinc ore, 'Calamine'). It is, therefore, somewhat ironic that zinc is a relatively late addition to the pantheon of signal ions in biology and medicine. However, the number of biological functions, health implications and pharmacological targets that are emerging for zinc indicate that it might turn out to be 'the calcium of the twenty-first century'.

The neurobiology of zinc in health and disease

ESPEN guideline on clinical nutrition in the intensive care unit

Molecular and cellular mechanisms of cadmium carcinogenesis

Compared to several other metal ions with similar chemical properties, zinc is relatively harmless. Only exposure to high doses has toxic effects, making acute zinc intoxication a rare event. In addition to acute intoxication, long-term, high-dose zinc supplementation interferes with the uptake of copper. Hence, many of its toxic effects are in fact due to copper deficiency. While systemic homeostasis and efficient regulatory mechanisms on the cellular level generally prevent the uptake of cytotoxic doses of exogenous zinc, endogenous zinc plays a significant role in cytotoxic events in single cells. Here, zinc influences apoptosis by acting on several molecular regulators of programmed cell death, including caspases and proteins from the Bcl and Bax families. One organ where zinc is prominently involved in cell death is the brain, and cytotoxicity in consequence of ischemia or trauma involves the accumulation of free zinc. Rather than being a toxic metal ion, zinc is an essential trace element. Whereas intoxication by excessive exposure is rare, zinc deficiency is widespread and has a detrimental impact on growth, neuronal development, and immunity, and in severe cases its consequences are lethal. Zinc deficiency caused by malnutrition and foods with low bioavailability, aging, certain diseases, or deregulated homeostasis is a far more common risk to human health than intoxication.

https://www.mdpi.com/1660-4601/7/4/1342/pdf

The Essential Toxin: Impact of Zinc on Human Health

Zinc is essential for cell proliferation and differentiation, especially for the regulation of DNA synthesis and mitosis. On the molecular level, it is a structural constituent of a great number of proteins, including enzymes of cellular signaling pathways and transcription factors. Zinc homeostasis in eukaryotic cells is controlled on the levels of uptake, intracellular sequestration in zinc storing vesicles ('zincosomes'), nucleocytoplasmic distribution and elimination. These processes involve the major zinc binding protein metallothionein as a tool for the regulation of the cellular zinc level and the nuclear translocation of zinc in the course of the cell cycle and differentiation. In addition, there is also increasing evidence for a direct signaling function for zinc on all levels of signal transduction. Zinc can modulate cellular signal recognition, second messenger metabolism, protein kinase and protein phosphatase activities, and it may stimulate or inhibit activities of transcription factors, depending on the experimental systems studied. Zinc has been shown to modify specifically the metabolism of cGMP, the activities of protein kinase C and mitogen activated protein kinases, and the activity of transcription factor MTF-1 which controls the transcription of the genes for metallothionein and the zinc transporter ZnT-1. As a conclusion of these observations new hypotheses regarding regulatory functions of zinc ions in cellular signaling pathways are proposed.

Functions of zinc in signaling, proliferation and differentiation of mammalian cells.

Recent years have brought a paradigm shift for the role of the essential trace element zinc in immunity. Although its function as a structural component of many enzymes has been known for decades, current experimental evidence points to an additional function of the concentration of free or loosely bound zinc ions as an intracellular signal. The activity of virtually all immune cells is modulated by zinc in vitro and in vivo. In this review, we discuss the interactions of zinc with major signaling pathways that regulate immune cell activity, and the implications of zinc deficiency or supplementation on zinc signaling as the molecular basis for an effect of zinc on immune cell function.

Functional Significance of Zinc-Related Signaling Pathways in Immune Cells

The trace element zinc is essential for the immune system, and zinc deficiency affects multiple aspects of innate and adaptive immunity. There are remarkable parallels in the immunological changes during aging and zinc deficiency, including a reduction in the activity of the thymus and thymic hormones, a shift of the T helper cell balance toward T helper type 2 cells, decreased response to vaccination, and impaired functions of innate immune cells. Many studies confirm a decline of zinc levels with age. Most of these studies do not classify the majority of elderly as zinc deficient, but even marginal zinc deprivation can affect immune function. Consequently, oral zinc supplementation demonstrates the potential to improve immunity and efficiently downregulates chronic inflammatory responses in the elderly. These data indicate that a wide prevalence of marginal zinc deficiency in elderly people may contribute to immunosenescence.

/pdf/the-immune-system-and-the-impact-of-zinc-during-aging-55nfxslnbf.pdf

Hajo Haase

Papers

The Essential Toxin: Impact of Zinc on Human Health

Functions of zinc in signaling, proliferation and differentiation of mammalian cells.

Functional Significance of Zinc-Related Signaling Pathways in Immune Cells

The immune system and the impact of zinc during aging

Zinc homeostasis and immunity