Selenium and brain function: a poorly recognized liaison

Schweizer, Ulrich; Bräuer, Anja U.; Köhrle, Josef; Nitsch, Robert; Savaskan, Nicolai Ε.

doi:10.1016/j.brainresrev.2004.03.004

Cited by 298 publications

(201 citation statements)

References 150 publications

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“…Furthermore, several studies reported that these proteins were tightly associated with a variety of chronic diseases. Glutathione peroxidase (GPX), thioredoxin reductase, methionine-sulfoxide-reductase and SelP are serious infection-related selenoproteins involved in antioxidant defense and intracellular redox regulation and modulation (3,4). Several selenoprotein activities have also been detected in the human and rodent brain.…”

Section: Introductionmentioning

confidence: 99%

“…Several selenoprotein activities have also been detected in the human and rodent brain. These activities were significantly altered in a number of neurological disorders, including epilepsy, Parkinson's disease, and Alzheimer's disease (3,5). In particular, considerable data from animals and humans have indicated that selenoprotein is effective in reducing the incidence of several different types of cancer, including cancers of the prostate and breast (6).…”

Section: Introductionmentioning

confidence: 99%

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Overexpression of human selenoprotein M differentially regulates the concentrations of antioxidants and H2O2, the activity of antioxidant enzymes, and the composition of white blood cells in a transgenic rat

Hwang¹,

Sin²,

Kim³

et al. 2008

Int J Mol Med

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Abstract. Selenoprotein is associated with a variety of serious diseases, including infectious diseases, neurodegenerative disorders, cancer and cardiovascular disease. The aim of this study was to produce a new transgenic (Tg) rat expressing human selenoprotein M (SelM) in order to examine the protective function of the antioxidant status in vivo. To achieve this, a new lineage of Tg rats was produced by the microinjection of pCMV/GFP-hSelM constructs into a fertilized rat egg. Several conclusions can be drawn based on the results of the present study. The human SelM gene was successfully expressed at both the transcription and protein levels in the CMV/GFP-hSelM Tg rats. This Tg rat showed a different enzyme activity for the antioxidant protein in the various tissues examined. In response to the 2,2'-azobiz(2-amidinopropane) dihydrochloride (AAPH) injection, the Tg rats showed a lower level of antioxidant and H 2 O 2 concentration as the activity of the antioxidant enzyme was maintained at a higher level in the Tg rats than in the non-Tg rats. Also, the neutrophil-to-lymphocyte ratio was significantly increased in this Tg rat, even though the level of corticosterone remained unchanged in both genotypes. Thus, the results of this study demonstrated that the CMV/GFP-hSelM Tg rat can serve as an animal model for the maintenance of a high level of antioxidant status and can be used to study the biological function of selenoprotein in infectious diseases, cardiovascular disease and cancer.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Overexpression of human selenoprotein M differentially regulates the concentrations of antioxidants and H2O2, the activity of antioxidant enzymes, and the composition of white blood cells in a transgenic rat

Hwang¹,

Sin²,

Kim³

et al. 2008

Int J Mol Med

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show abstract

“…Stem cell knockout of gpx4 leads to early embryonic lethality (Imai et al, 2003;Yant et al, 2003), whereas GPx1 knockout mice develop normally and are fully viable (Ho et al, 1997;de Haan et al, 1998). Interestingly, GPx4 shows a unique cellular distribution in brain compared to GPx1 (Ho et al, 1997;Schweizer et al, 2004;Savaskan et al, 2007). During embryonic development, GPx4 is expressed in principal neurons of the brain.…”

Section: Introductionmentioning

confidence: 99%

Molecular biology of glutathione peroxidase 4: from genomic structure to developmental expression and neural function

Savaskan

Ufer

Kühn

et al. 2007

BCHM

115

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Selenoproteins have been recognized as modulators of brain function and signaling. Phospholipid hydroperoxide glutathione peroxidase (GPx4/PHGPx) is a unique member of the selenium-dependent glutathione peroxidases in mammals with a pivotal role in brain development and function. GPx4 exists as a cytosolic, mitochondrial, and nuclear isoform derived from a single gene. In mice, the GPx4 gene is located on chromosome 10 in close proximity to a functional retrotransposome that is expressed under the control of captured regulatory elements. Elucidation of crystallographic data uncovered structural peculiarities of GPx4 that provide the molecular basis for its unique enzymatic properties and substrate specificity. Monomeric GPx4 is multifunctional: it acts as a reducing enzyme of peroxidized phospholipids and thiols and as a structural protein. Transcriptional regulation of the different GPx4 isoforms requires several isoform-specific cis-regulatory sequences and trans-activating factors. Cytosolic and mitochondrial GPx4 are the major isoforms exclusively expressed by neurons in the developing brain. In stark contrast, following brain trauma, GPx4 is specifically upregulated in non-neuronal cells, i.e., reactive astrocytes. Molecular approaches to genetic modification in mice have revealed an essential and isoform-specific function for GPx4 in development and disease. Here we review recent findings on GPx4 with emphasis on its molecular structure and function and consider potential mechanisms that underlie neural development and neuropathological conditions.

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“…Furthermore, SelW levels were significantly low in Se deficient diets, and its expression might be regulated by Se levels (Yeh et al, 1995(Yeh et al, , 1997Pagmantidis et al, 2005). The expression level was no significant in muscles and heart from human and sheep (Whanger, 2001;Schweizer et al, 2004), but CpSelW was constitutively expressed in tissues, and was predominantly expressed in the hepatopancreas, followed by gill and mantle, adductor muscle, and weak expression in the hemocytes. Under the conditions of bacterial challenge, the respiratory bursts in mollusk significantly increased and likely induced production of large amounts of reactive oxygen species (ROS) (Nakamura et al, 1985;Winston et al, 1996).…”

Section: Danio Rerio (Np_840072)mentioning

confidence: 99%

“…Selenoprotein W (SelW) is a small selenoprotein that contains one selenocysteine residue, and it was first known in sheep suffering from selenium deficiency (Sun et al, 2001), and is major expressed in muscle and heart in mammals (Whanger, 2001;Schweizer et al, 2004). SelW is capable of binding reduced glutathione (GSH) (Jeong et al, 2002), and overexpression of SelW experiment suggested that it may be an important component of the cellular defense system against oxidative stress (Sun et al, 2001).…”

Section: Introductionmentioning

confidence: 99%