The Thioredoxin-Like Family of Selenoproteins: Implications in Aging and Age-Related Degeneration
- 97 Downloads
The thioredoxin-like (Rdx) family proteins contain four selenoproteins (selenoprotein H, SELENOH; selenoprotein T, SELENOT; selenoprotein V, SELENOV; selenoprotein W, SELENOW) and a nonselenoprotein Rdx12. They share a CxxU or a CxxC (C, cysteine; x, any amino acid; U, selenocysteine) motif and a stretch of eGxFEI(V) sequence. From the evolutionary perspective, SELENOW and SELENOV are clustered together and SELENOH and SELENOT are in another branch. Selenoproteins in the Rdx family exhibit tissue- and organelle-specific distribution and are differentially influenced in response to selenium deficiency. While SELENOH is nucleus-exclusive, SELENOT resides mainly in endoplasmic reticulum and SELENOW in cytosol. SELENOV is expressed essentially only in the testes with unknown cellular localization. SELENOH and SELENOW are more sensitive than SELENOT and SELENOV to selenium deficiency. While physiological functions of the Rdx family of selenoproteins are not fully understand, results from animal models demonstrated that (1) brain-specific SELENOT knockout mice are susceptible to 1-methyl-4-phenylpyridinium-induced Parkinson’s disease in association with redox imbalance and (2) adult zebrafishes with heterozygous SELENOH knockout are prone to dimethylbenzanthracene-induced tumorigenesis together with increased DNA damage and oxidative stress. Further animal and human studies are needed to fully understand physiological roles of the Rdx family of selenoproteins in redox regulation, genome maintenance, aging, and age-related degeneration.
KeywordsSelenium Selenoprotein H Selenoprotein T Selenoprotein W Selenoprotein V
This study is financially supported in part by the National Institute of Food and Agriculture (Multistate NE1439, accession no. 1008124, project no. MIS-384050), National Natural Science Foundation of China (81771510 to X Zhang), and Wenzhou Municipal Science and Technology Bureau (C20170003 to JH Zhu).
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflict of interest.
- 5.Zhang L, Zeng H, Cheng WH (2018) Beneficial and paradoxical roles of selenium at nutritional levels of intake in healthspan and longevity. Free Radic Biol Med doi. https://doi.org/10.1016/j.freeradbiomed.2018.05.067
- 6.Dikiy A, Novoselov SV, Fomenko DE, Sengupta A, Carlson BA, Cerny RL, Ginalski K, Grishin NV, Hatfield DL, Gladyshev VN (2007) SelT, SelW, SelH, and Rdx12: genomics and molecular insights into the functions of selenoproteins of a novel thioredoxin-like family. Biochemistry 46:6871–6882CrossRefGoogle Scholar
- 12.Tanguy Y, Falluel-Morel A, Arthaud S, Boukhzar L, Manecka DL, Chagraoui A, Prevost G, Elias S, Dorval-Coiffec I, Lesage J, Vieau D, Lihrmann I, Jegou B, Anouar Y (2011) The PACAP-regulated gene selenoprotein T is highly induced in nervous, endocrine, and metabolic tissues during ontogenetic and regenerative processes. Endocrinology 152:4322–4335CrossRefGoogle Scholar
- 14.Prevost G, Arabo A, Jian L, Quelennec E, Cartier D, Hassan S, Falluel-Morel A, Tanguy Y, Gargani S, Lihrmann I, Kerr-Conte J, Lefebvre H, Pattou F, Anouar Y (2013) The PACAP-regulated gene selenoprotein T is abundantly expressed in mouse and human beta-cells and its targeted inactivation impairs glucose tolerance. Endocrinology 154:3796–3806CrossRefGoogle Scholar
- 17.Chen XD, Zhao ZP, Zhou JC, Lei XG (2018) Evolution, regulation, and function of porcine selenogenome. Free Radic Biol Med doi. https://doi.org/10.1016/j.freeradbiomed.2018.04.560
- 18.Boukhzar L, Hamieh A, Cartier D, Tanguy Y, Alsharif I, Castex M, Arabo A, El Hajji S, Bonnet JJ, Errami M, Falluel-Morel A, Chagraoui A, Lihrmann I, Anouar Y (2016) Selenoprotein T exerts an essential oxidoreductase activity that protects dopaminergic neurons in mouse models of Parkinson’s disease. Antioxid Redox Signal 24:557–574Google Scholar
- 20.Grumolato L, Ghzili H, Montero-Hadjadje M, Gasman S, Lesage J, Tanguy Y, Galas L, Ait-Ali D, Leprince J, Guerineau NC, Elkahloun AG, Fournier A, Vieau D, Vaudry H, Anouar Y (2008) Selenoprotein T is a PACAP-regulated gene involved in intracellular Ca2+ mobilization and neuroendocrine secretion. FASEB J 22:1756–1768CrossRefGoogle Scholar
- 22.Castex MT, Arabo A, Benard M, Roy V, Le Joncour V, Prevost G, Bonnet JJ, Anouar Y, Falluel-Morel A (2016) Selenoprotein T deficiency leads to neurodevelopmental abnormalities and hyperactive behavior in mice. Mol Neurobiol 53:5818–5832Google Scholar
- 30.Cox AG, Tsomides A, Kim AJ, Saunders D, Hwang KL, Evason KJ, Heidel J, Brown KK, Yuan M, Lien EC, Lee BC, Nissim S, Dickinson B, Chhangawala S, Chang CJ, Asara JM, Houvras Y, Gladyshev VN, Goessling W (2016) Selenoprotein H is an essential regulator of redox homeostasis that cooperates with p53 in development and tumorigenesis. Proc Natl Acad Sci U S A 113:E5562–E5571CrossRefGoogle Scholar
- 31.Bertz M, Kuhn K, Koeberle SC, Muller MF, Hoelzer D, Thies K, Deubel S, Thierbach R, Kipp AP (2018) Selenoprotein H controls cell cycle progression and proliferation of human colorectal cancer cells. Free Radic Biol Med doi. https://doi.org/10.1016/j.freeradbiomed.2018.01.010
- 33.Behne D, Hofer T, von Berswordt-Wallrabe R, Elger W (1982) Selenium in the testis of the rat: studies on its regulation and its importance for the organism. J Nutr 112:1682–1687Google Scholar
- 34.Pitts MW, Kremer PM, Hashimoto AC, Torres DJ, Byrns CN, Williams CS, Berry MJ (2015) Competition between the brain and testes under selenium-compromised conditions: insight into sex differences in selenium metabolism and risk of neurodevelopmental disease. J Neurosci 35:15326–15338CrossRefGoogle Scholar
- 35.Tamura K, Ne M (1993) Estimation of the number of nucleotide substitutions in the control region of mitochondrial DNA in humans and chimpanzees. Mol Biol Evol 10:512–526Google Scholar