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L-ergothioneine reduces nitration of lactoferrin and loss of antibacterial activity associated with nitrosative stress

Lactoferrin (LF) is a multifunctional antimicrobial, anti-inflammatory, and antioxidant protein that occurs naturally in mammals, most notably in exocrine gland tissues and fluids, such as in the eye. Nitrosative stress can promote changes to tyrosine and other amino acid residues of the protein, wh...

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Autores principales: Alhalwani, Amani Y., Davey, Rachel L., Repine, John E., Huffman, J. Alex
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10023959/
https://www.ncbi.nlm.nih.gov/pubmed/36942322
http://dx.doi.org/10.1016/j.bbrep.2023.101447
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author Alhalwani, Amani Y.
Davey, Rachel L.
Repine, John E.
Huffman, J. Alex
author_facet Alhalwani, Amani Y.
Davey, Rachel L.
Repine, John E.
Huffman, J. Alex
author_sort Alhalwani, Amani Y.
collection PubMed
description Lactoferrin (LF) is a multifunctional antimicrobial, anti-inflammatory, and antioxidant protein that occurs naturally in mammals, most notably in exocrine gland tissues and fluids, such as in the eye. Nitrosative stress can promote changes to tyrosine and other amino acid residues of the protein, which also reduces the activity of LF. l-ergothioneine (ET) is a potent anti-inflammatory antioxidant present in the eye and other tissues through nutrition or supplementation and that may play a role in the prevention or treatment of a variety of diseases. Here we investigated the ability of ET to reduce 3-nitrotyrosine (NTyr) formation using two separate substrates, with the goal of determining whether ET can protect the antibacterial function of LF and other proteins when exposed separately to peroxynitrite and tetranitromethane as nitrating reagents. Native human LF was used as a simple protein substrate, and lamb corneal lysate was chosen as one example of mammalian tissue with a more complex mixture of proteins and other biomolecules. Nitration was monitored by absorbance and fluorescence spectroscopy as well as sandwich (nitrated LF) and direct NTyr (corneal lysate) enzyme-linked immunosorbent assays (ELISAs). We found that pretreatment with ET reduced chemical modification of both native LF and corneal lysate samples and loss of antibacterial LF function due to exposure to the nitrating reagents. These initial results suggest that ET, raised to sufficiently elevated levels, could be tailored as a therapeutic agent to reduce effects of nitrosative stress on LF and in turn sustain the protein activity.
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spelling pubmed-100239592023-03-19 L-ergothioneine reduces nitration of lactoferrin and loss of antibacterial activity associated with nitrosative stress Alhalwani, Amani Y. Davey, Rachel L. Repine, John E. Huffman, J. Alex Biochem Biophys Rep Research Article Lactoferrin (LF) is a multifunctional antimicrobial, anti-inflammatory, and antioxidant protein that occurs naturally in mammals, most notably in exocrine gland tissues and fluids, such as in the eye. Nitrosative stress can promote changes to tyrosine and other amino acid residues of the protein, which also reduces the activity of LF. l-ergothioneine (ET) is a potent anti-inflammatory antioxidant present in the eye and other tissues through nutrition or supplementation and that may play a role in the prevention or treatment of a variety of diseases. Here we investigated the ability of ET to reduce 3-nitrotyrosine (NTyr) formation using two separate substrates, with the goal of determining whether ET can protect the antibacterial function of LF and other proteins when exposed separately to peroxynitrite and tetranitromethane as nitrating reagents. Native human LF was used as a simple protein substrate, and lamb corneal lysate was chosen as one example of mammalian tissue with a more complex mixture of proteins and other biomolecules. Nitration was monitored by absorbance and fluorescence spectroscopy as well as sandwich (nitrated LF) and direct NTyr (corneal lysate) enzyme-linked immunosorbent assays (ELISAs). We found that pretreatment with ET reduced chemical modification of both native LF and corneal lysate samples and loss of antibacterial LF function due to exposure to the nitrating reagents. These initial results suggest that ET, raised to sufficiently elevated levels, could be tailored as a therapeutic agent to reduce effects of nitrosative stress on LF and in turn sustain the protein activity. Elsevier 2023-03-11 /pmc/articles/PMC10023959/ /pubmed/36942322 http://dx.doi.org/10.1016/j.bbrep.2023.101447 Text en © 2023 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research Article
Alhalwani, Amani Y.
Davey, Rachel L.
Repine, John E.
Huffman, J. Alex
L-ergothioneine reduces nitration of lactoferrin and loss of antibacterial activity associated with nitrosative stress
title L-ergothioneine reduces nitration of lactoferrin and loss of antibacterial activity associated with nitrosative stress
title_full L-ergothioneine reduces nitration of lactoferrin and loss of antibacterial activity associated with nitrosative stress
title_fullStr L-ergothioneine reduces nitration of lactoferrin and loss of antibacterial activity associated with nitrosative stress
title_full_unstemmed L-ergothioneine reduces nitration of lactoferrin and loss of antibacterial activity associated with nitrosative stress
title_short L-ergothioneine reduces nitration of lactoferrin and loss of antibacterial activity associated with nitrosative stress
title_sort l-ergothioneine reduces nitration of lactoferrin and loss of antibacterial activity associated with nitrosative stress
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10023959/
https://www.ncbi.nlm.nih.gov/pubmed/36942322
http://dx.doi.org/10.1016/j.bbrep.2023.101447
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