Barbagallo, Mario

Kolisek, Martin

Romani, Andrea

Touyz, Rhian M.

English

Enlighten: Publications

Editorial
Magnesium and Other Biometals in Oxidative Medicine and
Redox Biology
Martin Kolisek,1 Rhian M. Touyz,2 Andrea Romani,3 and Mario Barbagallo4
1Comenius University in Bratislava, Jessenius Medical Faculty in Martin, Biomedical Center Martin, Martin 03601, Slovakia
2University of Glasgow, Glasgow G12 8TA, UK
3Case Western Reserve University, Cleveland, OH 44116-4970, USA
4University of Palermo, Palermo 90144, Italy
Correspondence should be addressed to Martin Kolisek; martink@zedat.fu-berlin.de
Received 8 August 2017; Accepted 8 August 2017; Published 4 October 2017
Copyright © 2017 Martin Kolisek et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Magnesium (Mg) and also other biometals (BM) play an
essential role in regulating a plethora of biological processes
such as (1) metabolism of biomacromolecules, (2) cell divi-
sion and proliferation, (3) normal mitochondrial homeosta-
sis and energy production, (4) normal redox homeostasis,
(5) antioxidant signaling, and (6) crosstalk between major
signal cascades. However, exact molecular mechanisms
underlying the action of Mg or other BM in these processes
are often only partially understood. This may relate, in part,
to lack of sensitive and specific tools to assess Mg and BM
in biological systems and to relative lack of emphasis of Mg
and BM in clinical medicine.
Diabetes mellitus type 2 (DT2) might serve as an example.
Hypomagnesaemia has been identified in 9 to 40% of
DT2 patients in “Mg-focused” clinical trials. However,
Mg status in DT2 patients is rarely determined as routine
clinical practice.
Another example highlighting the importance of Mg
homeostasis in disease etiology is Parkinson disease (PD). It
is not yet clear whether chronic intracellular Mg deficiency
causes the disease itself but it is obvious that insufficient
dietary intake of Mg or its wasting (GIT, kidney) worsens
PD symptoms and accelerates its progression.
Manganese (Mn) is an essential trace element involved
in many physiological processes supporting growth and
development, and also neuronal functions. On the other
hand, pathological accumulation of Mn in the brain has
a detrimental, toxic effect on neurons. Dopaminergic neu-
rons in the substantia nigra are especially sensitive to Mn
toxicity; thus, accumulated Mn may cause manganism, a
disease condition with etiology almost identical with PD.
Even though copper (Cu) plays a role in multiple vital
enzymatic reactions and physiological processes, it is notori-
ously known for its essential role in redox homeostasis in
cells and consequently tissues and organs of the body. For
instance, decreased levels of protein-bound Cu may lead to
iron (Fe) accumulation in the brain, thus increased oxidative
stress (OS) that is hallmarking prevalence and progression of
neurodegenerative and psychiatric diseases. The two patho-
logical conditions resulting directly from the perturbed
transport of Cu in the body are Menkes disease (negatively
affected is the intestinal P-type ATPase ATP7A transporting
Cu+) and Wilson’s disease (negatively affected is the P-type
ATPase ATP7B transporting Cu+ that is localized within
trans-Golgi network of hepatocytes and brain cells).
BM not only are important for global biochemistry
and physiology of the body, but also have been popular
in the field of implantology. For example, low toxicity,
durability (when in alloys), and biodegradability made
out of Mg a “super-component” of materials that are used
for manufacturing of the latest generation of stents or
other biodegradable implants. The field of implantology
and implant material engineering is progressing rapidly,
and it is likely that the success of Mg will be followed
by other BM soon.
Processes maintaining normal mitochondrial homeo-
stasis (MH) are essential for life and involve reactive oxygen
species (ROS). Excess bioavailability of ROS (oxidative
Hindawi
Oxidative Medicine and Cellular Longevity
Volume 2017, Article ID 7428796, 2 pages
https://doi.org/10.1155/2017/7428796
stress) contribute to cell dysfunction, injury, and mitophagy/
autophagy. At the levels of cells and also the whole body, MH
deterioration leads to senescence and death. Certain organs
(especially those metabolically highly active, e.g., brain, heart,
muscles, and liver) are more prone to deterioration of MH
than others. Thus, natural ageing may be paralleled with
premature ageing of particular organs that often demon-
strates as progressive degenerative disease. The factors
behind premature ageing of any organ might be encoded
genetically, or they have epigenetic, or environmental
background, or a combination of all. Mild OS (e.g., Akt-
mediated mitochondrial OS) triggers mitophagy. Excessive,
strong OS leads to death of the cells. Disbalanced homeo-
stasis of redox-active BM such as Cu, Fe, Mn, Zn, and Mg
might have deleterious effects on MH. Therefore, parame-
ters defining status of the homeostasis of aforementioned
BM should be routinely considered by the clinicians to
project correctly an integrative clinical image of the patient
that is necessary to adjust the most appropriate therapy.
Similar to PD, Alzheimer’s disease (AD) has been linked
to excessive OS, disturbed BM homeostasis, and disturbed
MH. I.-M. Balmus et al. in their work assessed (1) levels of
Mn, Mg, and Fe, (2) activities of superoxide dismutase
and glutathione peroxidase, and (3) concentration of malon-
dialdehyde (lipid peroxidation marker) in blood sera of
healthy probands, sera of patients with mild cognitive
impairment (MCI), and blood sera of patients with diag-
nosed AD. These authors found increased lipid peroxidation,
low antioxidant defense, low Mg and Fe concentrations, and
high Mn levels in MCI and AD patients, in a gradual manner.
Outcomes of this study clearly demonstrate aberrant BM
homeostasis with OS in MCI and AD. Moreover, these
data may help to develop a predictive protocol that could
complement AD biomarkers that are already being tested
in large clinical trials.
Both, 3-hydroxyanthranilic acid (3-HANA) and 3-
hydroxykynurenine (3-HK) are intermediates in the
metabolism of tryptophan. 3-HANA was initially considered
neurotoxic but later identified as having a neuroprotective
effect with therapeutic potential in neuroinflamatory
disorders such as AD. On the other hand, elevated levels of
3-HK are having clear neurotoxic effects linked to
pathologies of AD and early stage Huntington disease (HD).
D. Ramírez-Ortega et al. studied the effect of 3-HANA and
3-HK on Cu toxicity in primocultures of rat astrocytes.
These authors identified both kynurenines (1) to potentiate
the Cu cytotoxicity in ROS-independent manner and (2)
to potentiate the effect of Cu on the decrease of
glutathione (GSH) levels. Kynurenine pathway (KP) plays
an important role in regulation of OS and inflammation,
and in pathologies of major neurodegenerative disorders.
Therefore, work of group around D. Ramírez-Ortega et al.
urges for further examination of the crosstalk between
metabolites of KP and homeostasis of Cu (and perhaps also
homeostasis of other BM).
I. Pilchova et al. discuss in their review involvement of
Mg regulation of cellular and mitochondrial functions
focusing their attention primarily on energy metabolism,
mitochondrial calcium (Ca2+) handling, and apoptosis.
This work provides an up-to-date topic and emphasizes the
importance of mitochondrial Mg homeostasis (MMH)
beyond mitochondria and that aberrant MMH may have
detrimental effects on cell. At several occasions, the impor-
tance of mitochondria-endoplasmic reticulum (ER) cross-
talk, in respect to Mg homeostasis and essential intracellular
processes, is being accentuated.
The central role of BM in the maintenance of oxidative
balance within the frame of metabolic and neurodegenerative
disorders is discussed by M. Pokusa and A. K. Trancikova.
The review highlights the intersection between etiopatholo-
gies of neurodegeneration and of metabolic disorders. It
also features ROS and disturbed BM homeostasis as being
causative (and perhaps also consecutive) hallmarks of the
aforementioned disease conditions.
As previously mentioned, Mg is also a focus of implan-
tology and biomaterial engineering due to its low toxicity
and biodegradability. Z. Liu et al. in their work highlight
unique properties of Mg and microbicide effect of silver
(Ag; Ag nanoparticles generate ROS in living biological
systems). By controlling the microstructure and increasing
the Ag content, authors obtained Mg-Ag alloys with good
antibacterial properties in harsh and dynamic conditions
and with almost equivalent cytocompatibility to human
primary osteoblasts as pure Mg.
Papers in this special issue highlight new exciting data,
comment, and synthesise the newest knowledge on Mg and
other BM in oxidative medicine and redox biology. We hope
that this special issue will attract broad readership in the field
spanning from neurodegenerative to metabolic disorders
and implantology. We would like to express our thanks
to all the authors, reviewers, and the editorial team for the
great support in making this special issue a reality.
Martin Kolisek
Rhian M. Touyz
Andrea Romani
Mario Barbagallo
2 Oxidative Medicine and Cellular Longevity
Submit your manuscripts at
https://www.hindawi.com
Stem Cells
International
Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014
Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014
MEDIATORS
INFLAMMATION
of
Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014
Behavioural 
Neurology
Endocrinology
International Journal of
Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014
Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014
Disease Markers
Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014
BioMed 
Research International
Oncology
Journal of
Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014
Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014
Oxidative Medicine and 
Cellular Longevity
Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014
PPAR Research
The Scientific 
World Journal
Hindawi Publishing Corporation 
http://www.hindawi.com Volume 2014
Immunology Research
Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014
Journal of
Obesity
Journal of
Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014
Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014
 Computational and  
Mathematical Methods 
in Medicine
Ophthalmology
Journal of
Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014
Diabetes Research
Journal of
Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014
Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014
Research and Treatment
AIDS
Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014
Gastroenterology 
Research and Practice
Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014
Parkinson’s 
Disease
Evidence-Based 
Complementary and 
Alternative Medicine
Volume 2014
Hindawi Publishing Corporation
http://www.hindawi.com


Magnesium and other biometals in oxidative medicine and redox biology

Martin Kolisek

Rhian M. Touyz

Andrea Romani

Mario Barbagallo

Crossref

Oxidative Medicine and Cellular Longevity

Magnesium and Other Biometals in Oxidative Medicine and Redox Biology

Archivio istituzionale della ricerca - Università di Palermo

Enlighten

EditorialMagnesium and Other Biometals in Oxidative Medicine andRedox BiologyMartin Kolisek,1 Rhian M. Touyz,2 Andrea Romani,3 and Mario Barbagallo41Comenius University in Bratislava, Jessenius Medical Faculty in Martin, Biomedical Center Martin, Martin 03601, Slovakia2University of Glasgow, Glasgow G12 8TA, UK3Case Western Reserve University, Cleveland, OH 44116-4970, USA4University of Palermo, Palermo 90144, ItalyCorrespondence should be addressed to Martin Kolisek; martink@zedat.fu-berlin.deReceived 8 August 2017; Accepted 8 August 2017; Published 4 October 2017Copyright © 2017 Martin Kolisek et al. This is an open access article distributed under the Creative Commons Attribution License,which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Magnesium (Mg) and also other biometals (BM) play anessential role in regulating a plethora of biological processessuch as (1) metabolism of biomacromolecules, (2) cell divi-sion and proliferation, (3) normal mitochondrial homeosta-sis and energy production, (4) normal redox homeostasis,(5) antioxidant signaling, and (6) crosstalk between majorsignal cascades. However, exact molecular mechanismsunderlying the action of Mg or other BM in these processesare often only partially understood. This may relate, in part,to lack of sensitive and speciﬁc tools to assess Mg and BMin biological systems and to relative lack of emphasis of Mgand BM in clinical medicine.Diabetes mellitus type 2 (DT2) might serve as an example.Hypomagnesaemia has been identiﬁed in 9 to 40% ofDT2 patients in “Mg-focused” clinical trials. However,Mg status in DT2 patients is rarely determined as routineclinical practice.Another example highlighting the importance of Mghomeostasis in disease etiology is Parkinson disease (PD). Itis not yet clear whether chronic intracellular Mg deﬁciencycauses the disease itself but it is obvious that insuﬃcientdietary intake of Mg or its wasting (GIT, kidney) worsensPD symptoms and accelerates its progression.Manganese (Mn) is an essential trace element involvedin many physiological processes supporting growth anddevelopment, and also neuronal functions. On the otherhand, pathological accumulation of Mn in the brain hasa detrimental, toxic eﬀect on neurons. Dopaminergic neu-rons in the substantia nigra are especially sensitive to Mntoxicity; thus, accumulated Mn may cause manganism, adisease condition with etiology almost identical with PD.Even though copper (Cu) plays a role in multiple vitalenzymatic reactions and physiological processes, it is notori-ously known for its essential role in redox homeostasis incells and consequently tissues and organs of the body. Forinstance, decreased levels of protein-bound Cu may lead toiron (Fe) accumulation in the brain, thus increased oxidativestress (OS) that is hallmarking prevalence and progression ofneurodegenerative and psychiatric diseases. The two patho-logical conditions resulting directly from the perturbedtransport of Cu in the body are Menkes disease (negativelyaﬀected is the intestinal P-type ATPase ATP7A transportingCu+) and Wilson’s disease (negatively aﬀected is the P-typeATPase ATP7B transporting Cu+ that is localized withintrans-Golgi network of hepatocytes and brain cells).BM not only are important for global biochemistryand physiology of the body, but also have been popularin the ﬁeld of implantology. For example, low toxicity,durability (when in alloys), and biodegradability madeout of Mg a “super-component” of materials that are usedfor manufacturing of the latest generation of stents orother biodegradable implants. The ﬁeld of implantologyand implant material engineering is progressing rapidly,and it is likely that the success of Mg will be followedby other BM soon.Processes maintaining normal mitochondrial homeo-stasis (MH) are essential for life and involve reactive oxygenspecies (ROS). Excess bioavailability of ROS (oxidativeHindawiOxidative Medicine and Cellular LongevityVolume 2017, Article ID 7428796, 2 pageshttps://doi.org/10.1155/2017/7428796stress) contribute to cell dysfunction, injury, and mitophagy/autophagy. At the levels of cells and also the whole body, MHdeterioration leads to senescence and death. Certain organs(especially those metabolically highly active, e.g., brain, heart,muscles, and liver) are more prone to deterioration of MHthan others. Thus, natural ageing may be paralleled withpremature ageing of particular organs that often demon-strates as progressive degenerative disease. The factorsbehind premature ageing of any organ might be encodedgenetically, or they have epigenetic, or environmentalbackground, or a combination of all. Mild OS (e.g., Akt-mediated mitochondrial OS) triggers mitophagy. Excessive,strong OS leads to death of the cells. Disbalanced homeo-stasis of redox-active BM such as Cu, Fe, Mn, Zn, and Mgmight have deleterious eﬀects on MH. Therefore, parame-ters deﬁning status of the homeostasis of aforementionedBM should be routinely considered by the clinicians toproject correctly an integrative clinical image of the patientthat is necessary to adjust the most appropriate therapy.Similar to PD, Alzheimer’s disease (AD) has been linkedto excessive OS, disturbed BM homeostasis, and disturbedMH. I.-M. Balmus et al. in their work assessed (1) levels ofMn, Mg, and Fe, (2) activities of superoxide dismutaseand glutathione peroxidase, and (3) concentration of malon-dialdehyde (lipid peroxidation marker) in blood sera ofhealthy probands, sera of patients with mild cognitiveimpairment (MCI), and blood sera of patients with diag-nosed AD. These authors found increased lipid peroxidation,low antioxidant defense, low Mg and Fe concentrations, andhigh Mn levels in MCI and AD patients, in a gradual manner.Outcomes of this study clearly demonstrate aberrant BMhomeostasis with OS in MCI and AD. Moreover, thesedata may help to develop a predictive protocol that couldcomplement AD biomarkers that are already being testedin large clinical trials.Both, 3-hydroxyanthranilic acid (3-HANA) and 3-hydroxykynurenine (3-HK) are intermediates in themetabolism of tryptophan. 3-HANA was initially consideredneurotoxic but later identiﬁed as having a neuroprotectiveeﬀect with therapeutic potential in neuroinﬂamatorydisorders such as AD. On the other hand, elevated levels of3-HK are having clear neurotoxic eﬀects linked topathologies of AD and early stage Huntington disease (HD).D. Ramírez-Ortega et al. studied the eﬀect of 3-HANA and3-HK on Cu toxicity in primocultures of rat astrocytes.These authors identiﬁed both kynurenines (1) to potentiatethe Cu cytotoxicity in ROS-independent manner and (2)to potentiate the eﬀect of Cu on the decrease ofglutathione (GSH) levels. Kynurenine pathway (KP) playsan important role in regulation of OS and inﬂammation,and in pathologies of major neurodegenerative disorders.Therefore, work of group around D. Ramírez-Ortega et al.urges for further examination of the crosstalk betweenmetabolites of KP and homeostasis of Cu (and perhaps alsohomeostasis of other BM).I. Pilchova et al. discuss in their review involvement ofMg regulation of cellular and mitochondrial functionsfocusing their attention primarily on energy metabolism,mitochondrial calcium (Ca2+) handling, and apoptosis.This work provides an up-to-date topic and emphasizes theimportance of mitochondrial Mg homeostasis (MMH)beyond mitochondria and that aberrant MMH may havedetrimental eﬀects on cell. At several occasions, the impor-tance of mitochondria-endoplasmic reticulum (ER) cross-talk, in respect to Mg homeostasis and essential intracellularprocesses, is being accentuated.The central role of BM in the maintenance of oxidativebalance within the frame of metabolic and neurodegenerativedisorders is discussed by M. Pokusa and A. K. Trancikova.The review highlights the intersection between etiopatholo-gies of neurodegeneration and of metabolic disorders. Italso features ROS and disturbed BM homeostasis as beingcausative (and perhaps also consecutive) hallmarks of theaforementioned disease conditions.As previously mentioned, Mg is also a focus of implan-tology and biomaterial engineering due to its low toxicityand biodegradability. Z. Liu et al. in their work highlightunique properties of Mg and microbicide eﬀect of silver(Ag; Ag nanoparticles generate ROS in living biologicalsystems). By controlling the microstructure and increasingthe Ag content, authors obtained Mg-Ag alloys with goodantibacterial properties in harsh and dynamic conditionsand with almost equivalent cytocompatibility to humanprimary osteoblasts as pure Mg.Papers in this special issue highlight new exciting data,comment, and synthesise the newest knowledge on Mg andother BM in oxidative medicine and redox biology. We hopethat this special issue will attract broad readership in the ﬁeldspanning from neurodegenerative to metabolic disordersand implantology. We would like to express our thanksto all the authors, reviewers, and the editorial team for thegreat support in making this special issue a reality.Martin KolisekRhian M. TouyzAndrea RomaniMario Barbagallo2 Oxidative Medicine and Cellular LongevitySubmit your manuscripts athttps://www.hindawi.comStem CellsInternationalHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014MEDIATORSINFLAMMATIONofHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Behavioural NeurologyEndocrinologyInternational Journal ofHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Disease MarkersHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014BioMed Research InternationalOncologyJournal ofHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Oxidative Medicine and Cellular LongevityHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014PPAR ResearchThe Scientific World JournalHindawi Publishing Corporation http://www.hindawi.com Volume 2014Immunology ResearchHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Journal ofObesityJournal ofHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014 Computational and  Mathematical Methods in MedicineOphthalmologyJournal ofHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Diabetes ResearchJournal ofHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Research and TreatmentAIDSHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Gastroenterology Research and PracticeHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Parkinson’s DiseaseEvidence-Based Complementary and Alternative MedicineVolume 2014Hindawi Publishing Corporationhttp://www.hindawi.com

https://iris.unipa.it/bitstream/10447/297095/1/7428796.pdf

Magnesium and other biometals in oxidative medicine and redox biology

Abstract

Similar works

Full text

Available Versions

Enlighten: Publications

Crossref

Archivio istituzionale della ricerca - Università di Palermo

Enlighten