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Ni(II) Ions May Target the Entire Melatonin Biosynthesis Pathway—A Plausible Mechanism of Nickel Toxicity

Nickel is toxic to humans. Its compounds are carcinogenic. Furthermore, nickel allergy is a severe health problem that affects approximately 10–20% of humans. The mechanism by which these conditions develop remains unclear, but it may involve the cleavage of specific proteins by nickel ions. Ni(II)...

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Autores principales: Wezynfeld, Nina E., Bonna, Arkadiusz M., Płonka, Dawid, Bal, Wojciech, Frączyk, Tomasz
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9458082/
https://www.ncbi.nlm.nih.gov/pubmed/36080347
http://dx.doi.org/10.3390/molecules27175582
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author Wezynfeld, Nina E.
Bonna, Arkadiusz M.
Płonka, Dawid
Bal, Wojciech
Frączyk, Tomasz
author_facet Wezynfeld, Nina E.
Bonna, Arkadiusz M.
Płonka, Dawid
Bal, Wojciech
Frączyk, Tomasz
author_sort Wezynfeld, Nina E.
collection PubMed
description Nickel is toxic to humans. Its compounds are carcinogenic. Furthermore, nickel allergy is a severe health problem that affects approximately 10–20% of humans. The mechanism by which these conditions develop remains unclear, but it may involve the cleavage of specific proteins by nickel ions. Ni(II) ions cleave the peptide bond preceding the Ser/Thr-Xaa-His sequence. Such sequences are present in all four enzymes of the melatonin biosynthesis pathway, i.e., tryptophan 5-hydroxylase 1, aromatic-l-amino-acid decarboxylase, serotonin N-acetyltransferase, and acetylserotonin O-methyltransferase. Moreover, fragments prone to Ni(II) are exposed on surfaces of these proteins. Our results indicate that all four studied fragments undergo cleavage within tens of hours at pH 8.2 and 37 °C, corresponding with the conditions in the mitochondrial matrix. Since melatonin, a potent antioxidant and anti-inflammatory agent, is synthesized within the mitochondria of virtually all human cells, depleting its supply may be detrimental, e.g., by raising the oxidative stress level. Intriguingly, Ni(II) ions have been shown to mimic hypoxia through the stabilization of HIF-1α protein, but melatonin prevents the action of HIF-1α. Considering all this, the enzymes of the melatonin biosynthesis pathway seem to be a toxicological target for Ni(II) ions.
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spelling pubmed-94580822022-09-09 Ni(II) Ions May Target the Entire Melatonin Biosynthesis Pathway—A Plausible Mechanism of Nickel Toxicity Wezynfeld, Nina E. Bonna, Arkadiusz M. Płonka, Dawid Bal, Wojciech Frączyk, Tomasz Molecules Article Nickel is toxic to humans. Its compounds are carcinogenic. Furthermore, nickel allergy is a severe health problem that affects approximately 10–20% of humans. The mechanism by which these conditions develop remains unclear, but it may involve the cleavage of specific proteins by nickel ions. Ni(II) ions cleave the peptide bond preceding the Ser/Thr-Xaa-His sequence. Such sequences are present in all four enzymes of the melatonin biosynthesis pathway, i.e., tryptophan 5-hydroxylase 1, aromatic-l-amino-acid decarboxylase, serotonin N-acetyltransferase, and acetylserotonin O-methyltransferase. Moreover, fragments prone to Ni(II) are exposed on surfaces of these proteins. Our results indicate that all four studied fragments undergo cleavage within tens of hours at pH 8.2 and 37 °C, corresponding with the conditions in the mitochondrial matrix. Since melatonin, a potent antioxidant and anti-inflammatory agent, is synthesized within the mitochondria of virtually all human cells, depleting its supply may be detrimental, e.g., by raising the oxidative stress level. Intriguingly, Ni(II) ions have been shown to mimic hypoxia through the stabilization of HIF-1α protein, but melatonin prevents the action of HIF-1α. Considering all this, the enzymes of the melatonin biosynthesis pathway seem to be a toxicological target for Ni(II) ions. MDPI 2022-08-30 /pmc/articles/PMC9458082/ /pubmed/36080347 http://dx.doi.org/10.3390/molecules27175582 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wezynfeld, Nina E.
Bonna, Arkadiusz M.
Płonka, Dawid
Bal, Wojciech
Frączyk, Tomasz
Ni(II) Ions May Target the Entire Melatonin Biosynthesis Pathway—A Plausible Mechanism of Nickel Toxicity
title Ni(II) Ions May Target the Entire Melatonin Biosynthesis Pathway—A Plausible Mechanism of Nickel Toxicity
title_full Ni(II) Ions May Target the Entire Melatonin Biosynthesis Pathway—A Plausible Mechanism of Nickel Toxicity
title_fullStr Ni(II) Ions May Target the Entire Melatonin Biosynthesis Pathway—A Plausible Mechanism of Nickel Toxicity
title_full_unstemmed Ni(II) Ions May Target the Entire Melatonin Biosynthesis Pathway—A Plausible Mechanism of Nickel Toxicity
title_short Ni(II) Ions May Target the Entire Melatonin Biosynthesis Pathway—A Plausible Mechanism of Nickel Toxicity
title_sort ni(ii) ions may target the entire melatonin biosynthesis pathway—a plausible mechanism of nickel toxicity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9458082/
https://www.ncbi.nlm.nih.gov/pubmed/36080347
http://dx.doi.org/10.3390/molecules27175582
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