Abstract
Selenium, an essential micronutrient, plays vital roles in the brain. Selenoprotein P (SELENOP), a major plasma selenoprotein, is thought to transport selenium to the brain. However, Selenop-knockout mice fed a diet containing an adequate amount of selenium shows no objective neurological dysfunction which is observed in the selenium-deficient diet-fed Selenop-knockout mice. This fact indicated that selenium from low-mass selenium-source compounds can be transported by SELENOP-independent alternative pathways to the brain. In this study, to obtain the basic information about the SELENOP-independent transport pathways, we performed ex vivo experiments in which the rat brain cell membrane fraction was analyzed to find selenium-binding and/or -interactive proteins using its reactive metabolic intermediate, selenotrisulfide (STS), and MALDI TOF-mass spectrometry. Several membrane proteins with the cysteine (C) thiol were found to be reactive with STS through the thiol-exchange reaction. One of the C-containing proteins in the brain cell membrane fraction was identified as peptidyl-prolyl cis–trans isomerase (PPIase) A from tryptic fragmentation experiments and database search. Among the 4 C residues in rat PPIase A, 21st C was proved to react with STS by assessment using C mutated recombinant proteins. PPIase A is ubiquitously expressed and also associates with a variety of biologically important events such as immunomodulation, intracellular signaling, transcriptional regulation and protein trafficking. Consequently, PPIase A was thought to participate in the selenium transport into the rat brain.
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Abbreviations
- A:
-
L-Alanine
- C:
-
L-Cysteine
- DAN:
-
2,3-Diaminonaphthalene
- DTNB:
-
5,5′-Dithiobis(2-nitrobenzoic acid)
- GPX:
-
Glutathione peroxidase
- GSH:
-
Glutathione in reduced form
- GSSG:
-
Glutathione in oxidized form
- GSSeSG:
-
Glutathione selenotrisulfide
- MALDI TOF-MS:
-
Matrix-assisted laser desorption ionization time of flight-mass spectrometry
- NEM:
-
N-Ethylmaleimide
- Pen:
-
L-Penicillamine
- PenSSeSPen:
-
L-Penicillamine selenotrisulfide
- PPIase:
-
Peptidyl-prolyl cis–trans isomerase
- SELENOP:
-
Selenoprotein P
- STS:
-
Selenotrisulfide
- U:
-
L-Selenocysteine
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Acknowledgements
This study was supported by JSPS KAKENHI Grant number JP16K18921 and JP19K16351. This study was the result of using research equipment shared in the MEXT Project for promoting public utilization of advanced research infrastructure (Program for supporting introduction of the new sharing system) Grant number JPMXS0422500320.
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Yoshida, S., Yamamoto, A., Masumoto, H. et al. Peptidyl-prolyl cis–trans isomerase A participates in the selenium transport into the rat brain. J Biol Inorg Chem 26, 933–945 (2021). https://doi.org/10.1007/s00775-021-01903-6
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DOI: https://doi.org/10.1007/s00775-021-01903-6