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Biomolecules
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Zinc in Health and Disease Conditions
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Zinc in Health and Disease Conditions

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Medicine".

Deadline for manuscript submissions: closed (10 January 2023) | Viewed by 51128

Special Issue Editor

Dr. Xiang-Ping Chu

E-Mail Website
Guest Editor
Department(s) of Biomedical Sciences, School of Medicine, University of Missouri-Kansas City, Kansas City, MO 64108-2792, USA
Interests: acid-sensing ion channel; zinc; glucose; patch-clamp recording; stroke; drug addiction; brain injury
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Zinc, the 2nd most prevalent trace element in the body, functions as a signaling molecule that regulates a variety of physiological activities. Evidence from both basic and clinical studies suggests the importance of zinc homeostasis in physiological condition and disease states. For example, zinc, via modulation of a variety of targets, is critical for maintaining the balance between neuronal excitation and inhibition, while an imbalance between excitation and inhibition underlies seizures. However, the relationship between zinc signaling and disease states is complex, as both extracellular and intracellular zinc may produce either protective or detrimental effects. This Special Issue welcomes studies that provide functional (cellular and molecular) evidence on the involvement of zinc in physiology, pathology or pharmacology, as well as exploration into the potential of targeting biomolecules associated with zinc signaling or homeostasis as a therapeutic strategy. Original manuscripts and reviews dealing with any aspects of zinc are also encouraged.

Dr. Xiang-Ping Chu
Guest Editor

Manuscript Submission Information

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Keywords

  • zinc
  • physiology
  • disease
  • regulation/modulation
  • function
  • pathology

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Related Special Issue

Published Papers (11 papers)

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Research

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12 pages, 1776 KiB  
Article
No Association of Hair Zinc Concentration with Coronary Artery Disease Severity and No Relation with Acute Coronary Syndromes
by Ewelina A. Dziedzic, Jakub S. Gąsior, Agnieszka Tuzimek, Justyna Paleczny, Mirosław Kwaśny, Marek Dąbrowski and Piotr Jankowski
Biomolecules 2022, 12(7), 862; https://doi.org/10.3390/biom12070862 - 21 Jun 2022
Cited by 8 | Viewed by 2471
Abstract
Cardiovascular diseases (CVDs) are the leading cause of death worldwide. Although zinc (Zn) was reported to have antioxidant, anti-inflammatory and protective properties in CVDs, its association with coronary artery disease (CAD) is still unclear. As methods commonly used to assess Zn levels in [...] Read more.
Cardiovascular diseases (CVDs) are the leading cause of death worldwide. Although zinc (Zn) was reported to have antioxidant, anti-inflammatory and protective properties in CVDs, its association with coronary artery disease (CAD) is still unclear. As methods commonly used to assess Zn levels in blood and urine do not show the full picture of the microelement supply, in this study, the nutritional status of Zn in patients with angiographically confirmed CAD was assessed using inductively coupled plasma optical emission spectrometry. We found no association between Zn and the severity of CAD evaluated with the Coronary Artery Surgery Study Score (p = 0.67). There were no statistically significant differences in Zn levels between patients with acute coronary syndrome and those with stable CAD (p = 0.937). A statically significant negative correlation was observed between Zn content and serum triglyceride concentration (p < 0.05). Patients with type 2 diabetes mellitus were found to have a significantly lower hair Zn content compared to non-diabetic individuals (p < 0.01). The role of Zn in the pathogenesis of CAD and its complications need further well-designed research as the moderation and supplementation of Zn dietary intake could be a simple intervention to reduce the CVDs risk. Full article
(This article belongs to the Special Issue Zinc in Health and Disease Conditions)
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13 pages, 4312 KiB  
Article
Exacerbation of Elastase-Induced Emphysema via Increased Oxidative Stress in Metallothionein-Knockout Mice
by Ken Ichiro Tanaka, Sachie Shiota, Okina Sakakibara, Mikako Shimoda, Ayaka Takafuji, Misaki Takabatake, Yoshito Kadota, Takashige Kawakami, Shinya Suzuki and Masahiro Kawahara
Biomolecules 2022, 12(4), 583; https://doi.org/10.3390/biom12040583 - 15 Apr 2022
Cited by 8 | Viewed by 2674
Abstract
Although the pathogenesis of chronic obstructive pulmonary disease (COPD) is not yet fully understood, recent studies suggest that the disruption of the intracellular balance of oxidative (such as reactive oxygen species (ROS)) and antioxidant molecules plays an important role in COPD development and [...] Read more.
Although the pathogenesis of chronic obstructive pulmonary disease (COPD) is not yet fully understood, recent studies suggest that the disruption of the intracellular balance of oxidative (such as reactive oxygen species (ROS)) and antioxidant molecules plays an important role in COPD development and progression. Metallothionein is an endogenous metal-binding protein with reported ROS scavenging activity. Although there have been many publications on the protective effects of metallothionein in the kidney and liver, its role in COPD models such as elastase- or cigarette smoke (CS)-induced lung injury is unknown. Thus, in the present study, we analyzed the elastase-induced lung injury model using metallothionein-knockout (MT-KO; MT-1 and -2 gene deletion) mice. The expression of MT-1 and MT-2 in the lungs of MT-KO mice was markedly lower compared with that in the lungs of wildtype (WT) mice. Porcine pancreatic elastase (PPE)-induced lung injury (alveolar enlargement and respiratory impairment) was significantly exacerbated in MT-KO mice compared with WT mice. Additionally, PPE-induced increases in the number of inflammatory cells, inflammatory cytokines, and cell death in lung tissue were significantly more pronounced in MT-KO mice compared with WT mice. Finally, using an in vivo imaging system, we also found that PPE-induced ROS production in the lungs was enhanced in MT-KO mice compared with WT mice. These results suggest that metallothionein may act as an inhibitor against elastase-induced lung injury by suppressing ROS production. These results suggest that metallothionein protein, or compounds that can induce metallothionein, could be useful in the treatment of COPD. Full article
(This article belongs to the Special Issue Zinc in Health and Disease Conditions)
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Review

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15 pages, 1538 KiB  
Review
Zinc Homeostasis: An Emerging Therapeutic Target for Neuroinflammation Related Diseases
by Shunfeng Liu, Nan Wang, Yaqian Long, Zhuan Wu and Shouhong Zhou
Biomolecules 2023, 13(3), 416; https://doi.org/10.3390/biom13030416 - 22 Feb 2023
Cited by 13 | Viewed by 2718
Abstract
Zinc is an indispensable trace element in the human body and plays an important role in regulating normal growth and development. Zinc homeostasis in the central nervous system is closely related to the development of neuroinflammation, and synaptic zinc homeostasis disorders affect zinc [...] Read more.
Zinc is an indispensable trace element in the human body and plays an important role in regulating normal growth and development. Zinc homeostasis in the central nervous system is closely related to the development of neuroinflammation, and synaptic zinc homeostasis disorders affect zinc homeostasis in the brain. Under the condition of synaptic zinc homeostasis, proper zinc supplementation improves the body’s immunity and inhibits neuroinflammation. Synaptic zinc homeostasis disorder in the brain promotes the occurrence and development of neuroinflammation. Cerebral ischemia and hypoxia cause a massive release of synaptic Zn2+ into the synaptic cleft, resulting in neurotoxicity and neuroinflammation. Synaptic zinc homeostasis disorder is a high-risk factor for neurodegenerative diseases. Maintaining cerebral zinc homeostasis suppresses the progression of neuroinflammation-mediated neurodegenerative diseases. This article reviews the relationship between brain zinc homeostasis and neuroinflammation and proposes that maintaining synaptic zinc homeostasis prevents neuroinflammation. Full article
(This article belongs to the Special Issue Zinc in Health and Disease Conditions)
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24 pages, 5303 KiB  
Review
The Role of Zinc in Modulating Acid-Sensing Ion Channel Function
by Amber W. Sun, Michelle H. Wu, Madhumathi Vijayalingam, Michael J. Wacker and Xiang-Ping Chu
Biomolecules 2023, 13(2), 229; https://doi.org/10.3390/biom13020229 - 24 Jan 2023
Cited by 8 | Viewed by 2618
Abstract
Acid-sensing ion channels (ASICs) are proton-gated, voltage-independent sodium channels widely expressed throughout the central and peripheral nervous systems. They are involved in synaptic plasticity, learning/memory, fear conditioning and pain. Zinc, an important trace metal in the body, contributes to numerous physiological functions, with [...] Read more.
Acid-sensing ion channels (ASICs) are proton-gated, voltage-independent sodium channels widely expressed throughout the central and peripheral nervous systems. They are involved in synaptic plasticity, learning/memory, fear conditioning and pain. Zinc, an important trace metal in the body, contributes to numerous physiological functions, with neurotransmission being of note. Zinc has been implicated in the modulation of ASICs by binding to specific sites on these channels and exerting either stimulatory or inhibitory effects depending on the ASIC subtype. ASICs have been linked to several neurological and psychological disorders, such as Alzheimer’s disease, Parkinson’s disease, ischemic stroke, epilepsy and cocaine addiction. Different ASIC isoforms contribute to the persistence of each of these neurological and psychological disorders. It is critical to understand how various zinc concentrations can modulate specific ASIC subtypes and how zinc regulation of ASICs can contribute to neurological and psychological diseases. This review elucidates zinc’s structural interactions with ASICs and discusses the potential therapeutic implications zinc may have on neurological and psychological diseases through targeting ASICs. Full article
(This article belongs to the Special Issue Zinc in Health and Disease Conditions)
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15 pages, 1028 KiB  
Review
The Important Role of Zinc in Neurological Diseases
by Zhe Li, Yang Liu, Ruixue Wei, V. Wee Yong and Mengzhou Xue
Biomolecules 2023, 13(1), 28; https://doi.org/10.3390/biom13010028 - 23 Dec 2022
Cited by 41 | Viewed by 8635
Abstract
Zinc is one of the most abundant metal ions in the central nervous system (CNS), where it plays a crucial role in both physiological and pathological brain functions. Zinc promotes antioxidant effects, neurogenesis, and immune system responses. From neonatal brain development to the [...] Read more.
Zinc is one of the most abundant metal ions in the central nervous system (CNS), where it plays a crucial role in both physiological and pathological brain functions. Zinc promotes antioxidant effects, neurogenesis, and immune system responses. From neonatal brain development to the preservation and control of adult brain function, zinc is a vital homeostatic component of the CNS. Molecularly, zinc regulates gene expression with transcription factors and activates dozens of enzymes involved in neuronal metabolism. During development and in adulthood, zinc acts as a regulator of synaptic activity and neuronal plasticity at the cellular level. There are several neurological diseases that may be affected by changes in zinc status, and these include stroke, neurodegenerative diseases, traumatic brain injuries, and depression. Accordingly, zinc deficiency may result in declines in cognition and learning and an increase in oxidative stress, while zinc accumulation may lead to neurotoxicity and neuronal cell death. In this review, we explore the mechanisms of brain zinc balance, the role of zinc in neurological diseases, and strategies affecting zinc for the prevention and treatment of these diseases. Full article
(This article belongs to the Special Issue Zinc in Health and Disease Conditions)
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29 pages, 1113 KiB  
Review
Zinc in Human Health and Infectious Diseases
by Martina Maywald and Lothar Rink
Biomolecules 2022, 12(12), 1748; https://doi.org/10.3390/biom12121748 - 24 Nov 2022
Cited by 48 | Viewed by 7964
Abstract
During the last few decades, the micronutrient zinc has proven to be an important metal ion for a well-functioning immune system, and thus also for a suitable immune defense. Nowadays, it is known that the main cause of zinc deficiency is malnutrition. In [...] Read more.
During the last few decades, the micronutrient zinc has proven to be an important metal ion for a well-functioning immune system, and thus also for a suitable immune defense. Nowadays, it is known that the main cause of zinc deficiency is malnutrition. In particular, vulnerable populations, such as the elderly in Western countries and children in developing countries, are often affected. However, sufficient zinc intake and homeostasis is essential for a healthy life, as it is known that zinc deficiency is associated with a multitude of immune disorders such as metabolic and chronic diseases, as well as infectious diseases such as respiratory infections, malaria, HIV, or tuberculosis. Moreover, the modulation of the proinflammatory immune response and oxidative stress is well described. The anti-inflammatory and antioxidant properties of zinc have been known for a long time, but are not comprehensively researched and understood yet. Therefore, this review highlights the current molecular mechanisms underlying the development of a pro-/ and anti-inflammatory immune response as a result of zinc deficiency and zinc supplementation. Additionally, we emphasize the potential of zinc as a preventive and therapeutic agent, alone or in combination with other strategies, that could ameliorate infectious diseases. Full article
(This article belongs to the Special Issue Zinc in Health and Disease Conditions)
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13 pages, 693 KiB  
Review
Zinc’s Association with the CmPn/CmP Signaling Network in Breast Cancer Tumorigenesis
by Mellisa Renteria, Ofek Belkin, Justin Aickareth, David Jang, Majd Hawwar and Jun Zhang
Biomolecules 2022, 12(11), 1672; https://doi.org/10.3390/biom12111672 - 11 Nov 2022
Cited by 7 | Viewed by 1963
Abstract
It is well-known that serum and cellular concentrations of zinc are altered in breast cancer patients. Specifically, there are notable zinc hyper-aggregates in breast tumor cells when compared to normal mammary epithelial cells. However, the mechanisms responsible for zinc accumulation and the consequences [...] Read more.
It is well-known that serum and cellular concentrations of zinc are altered in breast cancer patients. Specifically, there are notable zinc hyper-aggregates in breast tumor cells when compared to normal mammary epithelial cells. However, the mechanisms responsible for zinc accumulation and the consequences of zinc dysregulation are poorly understood. In this review, we detailed cellular zinc regulation/dysregulation under the influence of varying levels of sex steroids and breast cancer tumorigenesis to try to better understand the intricate relationship between these factors based on our current understanding of the CmPn/CmP signaling network. We also made some efforts to propose a relationship between zinc signaling and the CmPn/CmP signaling network. Full article
(This article belongs to the Special Issue Zinc in Health and Disease Conditions)
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25 pages, 756 KiB  
Review
Investigating the Role of Zinc in Atherosclerosis: A Review
by Tong Shen, Qing Zhao, Yumin Luo and Tao Wang
Biomolecules 2022, 12(10), 1358; https://doi.org/10.3390/biom12101358 - 23 Sep 2022
Cited by 14 | Viewed by 2899
Abstract
Zinc, an indispensable micronutrient for human health, might play an important role in the development of atherosclerosis. Zinc could be involved in the atherogenic process through interaction with atherogenic cells, such as endothelial cells (ECs), vascular smooth muscle cells (VSMCs), and immune cells. [...] Read more.
Zinc, an indispensable micronutrient for human health, might play an important role in the development of atherosclerosis. Zinc could be involved in the atherogenic process through interaction with atherogenic cells, such as endothelial cells (ECs), vascular smooth muscle cells (VSMCs), and immune cells. In addition, zinc also exerts important positive or negative functions in various atherosclerosis-related risk factors, including lipid metabolism, glucose metabolism, and blood pressure. Currently, evidence focusing on the relationship between zinc status and atherogenic risk factors has been well established, while the direct interaction between zinc and atherosclerosis has not been fully understood. In this review, we aimed to summarize the association between zinc and atherosclerosis and explore current findings on how zinc and zinc homeostasis-associated proteins act in the atherogenic processes. Full article
(This article belongs to the Special Issue Zinc in Health and Disease Conditions)
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31 pages, 1039 KiB  
Review
Zinc in Cognitive Impairment and Aging
by Ruize Sun, Jue Wang, Juan Feng and Bin Cao
Biomolecules 2022, 12(7), 1000; https://doi.org/10.3390/biom12071000 - 18 Jul 2022
Cited by 28 | Viewed by 6016
Abstract
Zinc, an essential micronutrient for life, was first discovered in 1869 and later found to be indispensable for the normal development of plants and for the normal growth of rats and birds. Zinc plays an important role in many physiological and pathological processes [...] Read more.
Zinc, an essential micronutrient for life, was first discovered in 1869 and later found to be indispensable for the normal development of plants and for the normal growth of rats and birds. Zinc plays an important role in many physiological and pathological processes in normal mammalian brain development, especially in the development of the central nervous system. Zinc deficiency can lead to neurodegenerative diseases, mental abnormalities, sleep disorders, tumors, vascular diseases, and other pathological conditions, which can cause cognitive impairment and premature aging. This study aimed to review the important effects of zinc and zinc-associated proteins in cognitive impairment and aging, to reveal its molecular mechanism, and to highlight potential interventions for zinc-associated aging and cognitive impairments. Full article
(This article belongs to the Special Issue Zinc in Health and Disease Conditions)
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15 pages, 5461 KiB  
Review
The Impact of Zinc and Zinc Homeostasis on the Intestinal Mucosal Barrier and Intestinal Diseases
by Yan Wan and Bingkun Zhang
Biomolecules 2022, 12(7), 900; https://doi.org/10.3390/biom12070900 - 27 Jun 2022
Cited by 42 | Viewed by 7826
Abstract
Zinc is an essential trace element for living organisms, and zinc homeostasis is essential for the maintenance of the normal physiological functions of cells and organisms. The intestine is the main location for zinc absorption and excretion, while zinc and zinc homeostasis is [...] Read more.
Zinc is an essential trace element for living organisms, and zinc homeostasis is essential for the maintenance of the normal physiological functions of cells and organisms. The intestine is the main location for zinc absorption and excretion, while zinc and zinc homeostasis is also of great significance to the structure and function of the intestinal mucosal barrier. Zinc excess or deficiency and zinc homeostatic imbalance are all associated with many intestinal diseases, such as IBD (inflammatory bowel disease), IBS (irritable bowel syndrome), and CRC (colorectal cancer). In this review, we describe the role of zinc and zinc homeostasis in the intestinal mucosal barrier and the relevance of zinc homeostasis to gastrointestinal diseases. Full article
(This article belongs to the Special Issue Zinc in Health and Disease Conditions)
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16 pages, 1061 KiB  
Review
Zinc in Regulating Protein Kinases and Phosphatases in Neurodegenerative Diseases
by Hui-Liang Zhang, Xiao-Chuan Wang and Rong Liu
Biomolecules 2022, 12(6), 785; https://doi.org/10.3390/biom12060785 - 4 Jun 2022
Cited by 4 | Viewed by 3877
Abstract
Zinc is essential for human growth and development. As a trace nutrient, zinc plays important roles in numerous signal transduction pathways involved in distinct physiologic or pathologic processes. Protein phosphorylation is a posttranslational modification which regulates protein activity, degradation, and interaction with other [...] Read more.
Zinc is essential for human growth and development. As a trace nutrient, zinc plays important roles in numerous signal transduction pathways involved in distinct physiologic or pathologic processes. Protein phosphorylation is a posttranslational modification which regulates protein activity, degradation, and interaction with other molecules. Protein kinases (PKs) and phosphatases (PPs), with their effects of adding phosphate to or removing phosphate from certain substrates, are master regulators in controlling the phosphorylation of proteins. In this review, we summarize the disturbance of zinc homeostasis and role of zinc disturbance in regulating protein kinases and protein phosphatases in neurodegenerative diseases, with the focus of that in Alzheimer’s disease, providing a new perspective for understanding the mechanisms of these neurologic diseases. Full article
(This article belongs to the Special Issue Zinc in Health and Disease Conditions)
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