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α1-Microglobulin Binds Illuminated Flavins and Has a Protective Effect Against Sublethal Riboflavin-Induced Damage in Retinal Epithelial Cells

Bergwik, Jesper LU and Åkerström, Bo LU (2020) In Frontiers in Physiology 11.
Abstract

Riboflavin (vitamin B2) is an important constituent of the prosthetic groups flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN), which are utilized as electron-carriers in energy metabolism. Excitation by UV-light leads to the generation of riboflavin radicals and reactive oxygen species (ROS), which can oxidize a wide range of biomolecules. The human protein α1-microglobulin (A1M) is a reductase and a radical scavenger, which can protect cells and matrix against oxidative damage. Here, we provide evidence of a molecular interaction between illuminated riboflavin and A1M, similar to the radical scavenging reactions previously seen between A1M and other organic radicals. Binding between riboflavin and A1M was... (More)

Riboflavin (vitamin B2) is an important constituent of the prosthetic groups flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN), which are utilized as electron-carriers in energy metabolism. Excitation by UV-light leads to the generation of riboflavin radicals and reactive oxygen species (ROS), which can oxidize a wide range of biomolecules. The human protein α1-microglobulin (A1M) is a reductase and a radical scavenger, which can protect cells and matrix against oxidative damage. Here, we provide evidence of a molecular interaction between illuminated riboflavin and A1M, similar to the radical scavenging reactions previously seen between A1M and other organic radicals. Binding between riboflavin and A1M was demonstrated by gel migration shift, UV-absorbance and fluorescence spectrum analysis. The reaction between A1M and UV-light illuminated riboflavin involved covalent modification of A1M and proteolytic release of an N-terminal part of the protein. Furthermore, A1M also inhibited the ROS-induced photoreduction reaction of riboflavin, in a reaction involving the free thiol group in position C34. Finally, the results show a protective effect of A1M, analyzed by gene expression rates of stress genes, against sublethal damage in retinal epithelial cells in culture. Together, our results suggest a new role of A1M as a scavenger of riboflavin radicals and ROS produced during illumination of riboflavin.

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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
antioxidant, FAD, oxidative stress, retina, riboflavin, skin, vitamin B2, α-microglobulin
in
Frontiers in Physiology
volume
11
article number
295
publisher
Frontiers Media S. A.
external identifiers
  • pmid:32300309
  • scopus:85083498603
ISSN
1664-042X
DOI
10.3389/fphys.2020.00295
language
English
LU publication?
yes
id
9c478a04-c54d-4a4e-b17c-428b4b8ad18a
date added to LUP
2020-05-07 11:41:21
date last changed
2024-03-20 09:09:13
@article{9c478a04-c54d-4a4e-b17c-428b4b8ad18a,
  abstract     = {{<p>Riboflavin (vitamin B2) is an important constituent of the prosthetic groups flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN), which are utilized as electron-carriers in energy metabolism. Excitation by UV-light leads to the generation of riboflavin radicals and reactive oxygen species (ROS), which can oxidize a wide range of biomolecules. The human protein α<sub>1</sub>-microglobulin (A1M) is a reductase and a radical scavenger, which can protect cells and matrix against oxidative damage. Here, we provide evidence of a molecular interaction between illuminated riboflavin and A1M, similar to the radical scavenging reactions previously seen between A1M and other organic radicals. Binding between riboflavin and A1M was demonstrated by gel migration shift, UV-absorbance and fluorescence spectrum analysis. The reaction between A1M and UV-light illuminated riboflavin involved covalent modification of A1M and proteolytic release of an N-terminal part of the protein. Furthermore, A1M also inhibited the ROS-induced photoreduction reaction of riboflavin, in a reaction involving the free thiol group in position C34. Finally, the results show a protective effect of A1M, analyzed by gene expression rates of stress genes, against sublethal damage in retinal epithelial cells in culture. Together, our results suggest a new role of A1M as a scavenger of riboflavin radicals and ROS produced during illumination of riboflavin.</p>}},
  author       = {{Bergwik, Jesper and Åkerström, Bo}},
  issn         = {{1664-042X}},
  keywords     = {{antioxidant; FAD; oxidative stress; retina; riboflavin; skin; vitamin B2; α-microglobulin}},
  language     = {{eng}},
  publisher    = {{Frontiers Media S. A.}},
  series       = {{Frontiers in Physiology}},
  title        = {{α<sub>1</sub>-Microglobulin Binds Illuminated Flavins and Has a Protective Effect Against Sublethal Riboflavin-Induced Damage in Retinal Epithelial Cells}},
  url          = {{http://dx.doi.org/10.3389/fphys.2020.00295}},
  doi          = {{10.3389/fphys.2020.00295}},
  volume       = {{11}},
  year         = {{2020}},
}