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Responses and Defense Mechanisms against Toxic Metals
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Responses and Defense Mechanisms against Toxic Metals

A special issue of Stresses (ISSN 2673-7140).

Deadline for manuscript submissions: closed (30 October 2021) | Viewed by 21538

Special Issue Editors

Prof. Dr. Soisungwan Satarug

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Guest Editor
Centre for Kidney Disease Research, Translational Research Institute, Woolloongabba, Brisbane, Australia
Interests: epidemiology of cadmium toxicity; genetic and nutritional influence of cadmium toxicity outcomes; cadmium toxicity in at-risk subpopulations; novel methods of measuring cadmium in tissues; reverse dosimetry
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Luigi Sanita' di Toppi

E-Mail Website
Guest Editor
Department of Biology, University of Pisa, Via Luca Ghini 13, 56126 Pisa, Italy
Interests: heavy metals; metal homeostasis; phytochelatins; phytochelatin synthase; glutathione; plant evolution; lichens
Special Issues, Collections and Topics in MDPI journals
Dr. Rocío Vicentefranqueira Rodríguez

E-Mail Website
Guest Editor
Departamento de Microbiología y Genética, Universidad de Salamanca, Salamanca, Spain
Interests: aspergillus fumigatus; zinc; transcription; regulation
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The cellular stress response is a universal reaction of cells to damage to macromolecules (nucleic acids, proteins, and lipids) caused by stressors. Although many responses are not strictly specific, several other stress-specific mechanisms are simultaneously activated to restore or re-establish homeostasis. This Stresses Special Issue calls for epidemiological and experimental studies that investigate animal, human, plant, photoautotrophic, fungal, bacterial and viral responses to metal and metalloids, namely, cadmium (Cd), lead (Pb), mercury (Hg), arsenic (As), etc., as well as excess/homeostatic levels of iron (Fe), copper (Cu), zinc (Zn), manganese (Mn), etc. These are all elements that have been mobilized from non-bioavailable geologic matrices to biologically accessible sources from which they can enter food chains. Indeed, they are not biodegradable, and thus they persist indefinitely in the environment, which facilitates their transfer to food chains. In particular, Cd and Pb in cereals, potatoes, and other vegetables contribute the most to the total intake of these toxic metals (https://encyclopedia.pub/3575), while seafood is a known dietary source of methylmercury.

Authors are invited and welcome to submit original research papers, reviews, and short communications. Topics may embrace fundamental cell functions that are responsive to any toxic metal(loid), including excess of metal micronutrients. Examples are heme biosynthesis, heme degradation, and the homeostatic regulation of nutritionally essential Fe, Zn, and Cu. Studies of genetic and nutritional influences on these stress-response and stress-defense mechanisms are favourable, as are those attempting to elucidate the interplay of nutrition, genetics, and the environment in all the above biological systems. Reports of methodological development to probe cellular stressor responses are also welcome.

Prof. Dr. Soisungwan Satarug
Prof. Dr. Luigi Sanita' di Toppi
Dr. Rocío Vicentefranqueira Rodríguez
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Stresses is an international peer-reviewed open access quarterly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1000 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • cadmium
  • lead
  • mercury
  • zinc
  • copper
  • iron
  • manganese
  • glutathione
  • heme
  • heme oxygenases
  • heme sensor
  • metallothionein
  • metal homeostasis
  • phytochelatins
  • phytochelatin synthase
  • stress-response mechanism
  • stress response element (StRE)
  • cadmium response element (CdRE)
  • metal response element (MRE)
  • reporter gene assay
  • gene-environment interaction
  • anti-oxidative system

Published Papers (6 papers)

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Research

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10 pages, 1669 KiB  
Article
Tools for In Vitro Propagation/Synchronization of the Liverwort Marchantia polymorpha and Application of a Validated HPLC-ESI-MS-MS Method for Glutathione and Phytochelatin Analysis
by Silvia Giardini, Erika Bellini, Elena Bandoni, Alessandro Saba and Luigi Sanità di Toppi
Stresses 2022, 2(1), 136-145; https://doi.org/10.3390/stresses2010010 - 24 Feb 2022
Cited by 2 | Viewed by 2661
Abstract
Bryophytes, due to their poikilohydric nature and peculiar traits, are useful and versatile organisms for studies on metal accumulation and detoxification in plants. Among bryophytes, the liverwort Marchantia polymorpha is an excellent candidate as a model organism, having a key role in plant [...] Read more.
Bryophytes, due to their poikilohydric nature and peculiar traits, are useful and versatile organisms for studies on metal accumulation and detoxification in plants. Among bryophytes, the liverwort Marchantia polymorpha is an excellent candidate as a model organism, having a key role in plant evolutionary history. In particular, M. polymorpha axenic cultivation of gametophytes offers several advantages, such as fast growth, easy propagation and high efficiency of crossing. Thus, the main purpose of this work was to promote and validate experimental procedures useful in the establishment of a standardized set-up of M. polymorpha gametophytes, as well as to study cadmium detoxification processes in terms of thiol-peptide production, detection and characterisation by HPLC-mass spectrometry. The results show how variations in the composition of the Murashige and Skoog medium impact the growth rate or development of this liverwort, and what levels of glutathione and phytochelatins are produced by gametophytes to counteract cadmium stress. Full article
(This article belongs to the Special Issue Responses and Defense Mechanisms against Toxic Metals)
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13 pages, 903 KiB  
Article
Antioxidant Enzyme Activities as Biomarkers of Cu and Pb Stress in Centella asiatica
by Chee Kong Yap, Wen Siang Tan, Koe Wei Wong, Ghim Hock Ong, Wan Hee Cheng, Rosimah Nulit, Mohd. Hafiz Ibrahim, Weiyun Chew, Franklin Berandah Edward, Hideo Okamura, Khalid Awadh Al-Mutairi, Salman Abdo Al-Shami, Moslem Sharifinia, Muskhazli Mustafa, Wah June Leong and Chen Feng You
Stresses 2021, 1(4), 253-265; https://doi.org/10.3390/stresses1040018 - 05 Nov 2021
Cited by 12 | Viewed by 2551
Abstract
The present study investigated the antioxidant enzyme activities (AEA) of ascorbate peroxidase (APX), catalase (CAT), guaiacol peroxidase (GPX), and superoxide dismutase (SOD) as biomarkers of Cu and Pb stress by using Centella asiatica grown in an experimental hydroponic condition. The results showed (i) [...] Read more.
The present study investigated the antioxidant enzyme activities (AEA) of ascorbate peroxidase (APX), catalase (CAT), guaiacol peroxidase (GPX), and superoxide dismutase (SOD) as biomarkers of Cu and Pb stress by using Centella asiatica grown in an experimental hydroponic condition. The results showed (i) higher accumulations of Cu and Pb in the roots of C. asiatica than those in the leaves, (ii) synergistic effects of Cu and Pb stress at higher metal-level exposures, and (iii) Cu and Pb stress triggered the increment of APX, CAT, GPX, and SOD levels in both the leaves and roots of C. asiatica. The increment of four AEA indicated that C. asiatica underwent oxidative stress caused by the production of reactive oxygen species when the plant was exposed to Cu and Pb. In order to prevent damages caused by Cu and Pb stress, the AEA system was heightened in C. asiatica, in which APX, CAT, GPX, and SOD can be used as biomarkers of Pb and Cu stress in the plant. Full article
(This article belongs to the Special Issue Responses and Defense Mechanisms against Toxic Metals)
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19 pages, 3130 KiB  
Article
Theoretical Three-Dimensional Zinc Complexes with Glutathione, Amino Acids and Flavonoids
by José Manuel Pérez de la Lastra, Celia Andrés-Juan, Francisco J. Plou and Eduardo Pérez-Lebeña
Stresses 2021, 1(3), 123-141; https://doi.org/10.3390/stresses1030011 - 28 Jul 2021
Cited by 1 | Viewed by 4023
Abstract
Zinc plays an important role in the regulation of many cellular functions; it is a signaling molecule involved in the transduction of several cascades in response to intra and extracellular stimuli. Labile zinc is a small fraction of total intracellular zinc, that is [...] Read more.
Zinc plays an important role in the regulation of many cellular functions; it is a signaling molecule involved in the transduction of several cascades in response to intra and extracellular stimuli. Labile zinc is a small fraction of total intracellular zinc, that is loosely bound to proteins and is easily interchangeable. At the cellular level, several molecules can bind labile zinc and promote its passage across lipophilic membranes. Such molecules are known as ionophores. Several of these compounds are known in the scientific literature, but most of them can be harmful to human health and are therefore not allowed for medical use. We here performed a theoretical three-dimensional study of known zinc ionophores, together with a computational energetic study and propose that some dietary flavonoids, glutathione and amino acids could form zinc complexes and facilitate the transport of zinc, with the possible biological implications and potential health benefits of these natural compounds. The study is based on obtaining a molecular conformational structure of the zinc complexes with the lowest possible energy content. The discovery of novel substances that act as zinc ionophores is an attractive research topic that offers exciting opportunities in medicinal chemistry. We propose that these novel complexes could be promising candidates for drug design to provide new solutions for conditions and diseases related to zinc deficiency or impairment derived from the dysregulation of this important metal. Full article
(This article belongs to the Special Issue Responses and Defense Mechanisms against Toxic Metals)
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13 pages, 1175 KiB  
Article
Gender Differences in Zinc and Copper Excretion in Response to Co-Exposure to Low Environmental Concentrations of Cadmium and Lead
by Soisungwan Satarug, Glenda C. Gobe, Pailin Ujjin and David A. Vesey
Stresses 2021, 1(1), 3-15; https://doi.org/10.3390/stresses1010002 - 30 Dec 2020
Cited by 4 | Viewed by 3719
Abstract
Disruption of the homeostasis of zinc (Zn) and copper (Cu) has been associated with nephrotoxicity of cadmium (Cd). Herein, we report the results of a cross sectional analysis of urinary excretion of Zn, Cu, Cd and lead (Pb) in 392 Thais (mean age [...] Read more.
Disruption of the homeostasis of zinc (Zn) and copper (Cu) has been associated with nephrotoxicity of cadmium (Cd). Herein, we report the results of a cross sectional analysis of urinary excretion of Zn, Cu, Cd and lead (Pb) in 392 Thais (mean age 33.6) living in an area of low-level environmental exposure to Cd and Pb, reflected by the respective median Cd and Pb excretion rates of 0.44 and 1.75 μg/g creatinine. Evidence for dysregulation of Zn and Cu homeostasis has emerged together with gender differentiated responses. In men, excretion rates for Zn and Cu were increased concomitantly, and their urinary Zn-to-Cu ratios were maintained. In women, only Cu excretion rose, causing a reduction in urinary Zn-to-Cu ratios. Only in women, urinary Zn-to-Cu ratios were associated with worse kidney function, assessed by estimated glomerular filtration rate (eGFR) (β = −7.76, p = 0.015). Only in men, a positive association was seen between eGFR and body iron stores, reflected by serum ferritin (β = 5.32, p = 0.030). Thus, co-exposure to Cd and Pb may disrupt the homeostasis of Zn and Cu more severely in women than men, while urinary Zn-to-Cu ratios and body iron stores can serve as predictors of an adverse effect of co-exposure to Cd and Pb. Full article
(This article belongs to the Special Issue Responses and Defense Mechanisms against Toxic Metals)
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Review

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12 pages, 3259 KiB  
Review
The Nitration of Proteins, Lipids and DNA by Peroxynitrite Derivatives-Chemistry Involved and Biological Relevance
by José Manuel Pérez de la Lastra, Celia Andrés Juan, Francisco J. Plou and Eduardo Pérez-Lebeña
Stresses 2022, 2(1), 53-64; https://doi.org/10.3390/stresses2010005 - 29 Jan 2022
Cited by 27 | Viewed by 3359
Abstract
In recent years, much interest has been generated by the idea that nitrosative stress plays a role in the aetiology of human diseases, such as atherosclerosis, inflammation, cancer, and neurological diseases. The chemical changes mediated by reactive nitrogen species (RNS) are detrimental to [...] Read more.
In recent years, much interest has been generated by the idea that nitrosative stress plays a role in the aetiology of human diseases, such as atherosclerosis, inflammation, cancer, and neurological diseases. The chemical changes mediated by reactive nitrogen species (RNS) are detrimental to cell function, because they can cause nitration, which can alter the structures of cellular proteins, DNA, and lipids, and hence, impair their normal function. One of the most potent biological nitrosative agents is peroxynitrite (ONOO−), which is produced when nitric oxide (•NO) and superoxide (•O2−) are combined at extremely rapid rates. Considering the plethora of oxidations by peroxynitrite, this makes peroxynitrite the most prevalent nitrating species responsible for protein, DNA, and lipids nitration in vivo. There is biochemical evidence to suggest that the interactions of the radicals NO and superoxide result in the formation of a redox system, which includes the reactions of nitrosation and nitration, and is a component of the complex cellular signalling network. However, the chemistry involved in the nitration process with peroxynitrite derivatives is poorly understood, particularly for biological molecules, such as DNA, proteins, and lipids. Here, we review the processes involved in the nitration of biomolecules, and provide a mechanistic explanation for the chemical reactions of NOS and nitrosative stress. This study reveals that these processes are based on a surprisingly simple and straightforward chemistry, with a fascinating influence on cellular physiology and pathology. Full article
(This article belongs to the Special Issue Responses and Defense Mechanisms against Toxic Metals)
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14 pages, 1586 KiB  
Review
The Evolving Role for Zinc and Zinc Transporters in Cadmium Tolerance and Urothelial Cancer
by Soisungwan Satarug, David A. Vesey and Glenda C. Gobe
Stresses 2021, 1(2), 105-118; https://doi.org/10.3390/stresses1020009 - 19 May 2021
Cited by 5 | Viewed by 3557
Abstract
Cadmium (Cd) is an environmental toxicant with serious public health consequences due to its persistence within arable soils, and the ease with which it enters food chains and then, accumulates in human tissues to induce a broad range of adverse health effects. The [...] Read more.
Cadmium (Cd) is an environmental toxicant with serious public health consequences due to its persistence within arable soils, and the ease with which it enters food chains and then, accumulates in human tissues to induce a broad range of adverse health effects. The present review focuses on the role of zinc (Zn), a nutritionally essential metal, to protect against the cytotoxicity and carcinogenicity of Cd in urinary bladder epithelial cells. The stress responses and defense mechanisms involving the low-molecular-weight metal binding protein, metallothionein (MT), are highlighted. The efflux and influx transporters of the ZnT and Zrt-/Irt-like protein (ZIP) gene families are discussed with respect to their putative role in retaining cellular Zn homeostasis. Among fourteen ZIP family members, ZIP8 and ZIP14 mediate Cd uptake by cells, while ZnT1 is among ten ZnT family members solely responsible for efflux of Zn (Cd), representing cellular defense against toxicity from excessively high Zn (Cd) intake. In theory, upregulation of the efflux transporter ZnT1 concomitant with the downregulation of influx transporters such as ZIP8 and ZIP14 can prevent Cd accumulation by cells, thereby increasing tolerance to Cd toxicity. To link the perturbation of Zn homeostasis, reflected by the aberrant expression of ZnT1, ZIP1, ZIP6, and ZIP10, with malignancy, tolerance to Cd toxicity acquired during Cd-induced transformation of a cell model of human urothelium, UROtsa, is discussed as a particular example. Full article
(This article belongs to the Special Issue Responses and Defense Mechanisms against Toxic Metals)
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