Dual Function of the Selenoprotein PHGPx During Sperm Maturation

Ursini, Fulvio; Heim, Sabina; Kieß, Michael; Maiorino, Matilde; Roveri, Antonella; Wissing, Josef; Flohé, Leopold

doi:10.1126/science.285.5432.1393

Cited by 811 publications

(554 citation statements)

References 38 publications

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“…PHGPx is a major component of capsule, a keratinous structure around the mitochondria of mid piece and play a crucial role in spermatogenesis [37]. Evidence suggests that PHGPx, controls the production of reactive oxygen species (ROS),that produced in small amounts by spermatozoa and maintenance the spermatozoa viability, but at high concentrations, are toxic [38].…”

Section: Discussionmentioning

confidence: 99%

A proteomic analysis on human sperm tail: comparison between normozoospermia and asthenozoospermia

Hashemitabar

Sabbagh

Orazizadeh

et al. 2015

J Assist Reprod Genet

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Purpose Asthenozoospermia is a common cause of human male infertility characterized by reduced sperm motility. The molecular mechanism that impairs sperm motility is not fully understood. This study proposed to identify novel biomarkers by focusing on sperm tail proteomic analysis of asthenozoospermic patients. Methods Sperm were isolated from normozoospermic and asthenozoospermic semen samples. Tail fractions were obtained by sonication followed by Percoll gradient. The proteins were extracted by solubilization and subjected to two-dimensional gel electrophoresis (2-DE); then, the spots were analyzed using Image Master 2D Platinum software. The significantly increased/ decreased amounts of proteins in the two groups were exploited by matrix-assisted laser desorption-ionization time-of-flight/ time-of-flight (MALDI-TOF-TOF) mass spectrometry. Results Three hundred ninety protein spots were detected in both groups. Twenty-one protein spots that had significantly altered amounts (p<0.05) were excised and exploited using MALDI-TOF-TOF mass spectrometry. They led to the identification of the following 14 unique proteins: Tubulin beta 2B; glutathione S-transferase Mu 3; keratin, type II cytoskeletal 1; outer dense fiber protein 2; voltage-dependent anionselective channel protein 2; A-kinase anchor protein 4; cytochrome c oxidase subunit 6B; sperm protein associated with the nucleus on the X chromosome B; phospholipid hydroperoxide glutathione peroxidase-mitochondrial; isoaspartyl peptidase/L-asparaginase; heat shock-related 70 kDa protein 2; stress-70 protein, mitochondrial; glyceraldehyde-3-phosphate dehydrogenase, testis-specific and clusterin. Conclusion Fourteen proteins present in different amounts in asthenozoospermic sperm tail samples were identified, four of which are reported here for the first time. These proteins might be used as markers for the better diagnosis of sperm dysfunctions, targets for male contraceptive development, and to predict embryo quality.

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Section: Discussionmentioning

confidence: 99%

A proteomic analysis on human sperm tail: comparison between normozoospermia and asthenozoospermia

Hashemitabar

Sabbagh

Orazizadeh

et al. 2015

J Assist Reprod Genet

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“…An explanation for these findings has recently been afforded by the work of Ursini and colleagues. 7 They found that a form of glutathione peroxidase (GPx4), believed to shield developing sperm cells from oxidative damage, polymerises in mature sperm into a structural protein in the mitochondrial capsule of the midpiece region. As GPx4 accounts for about 50% of the capsule material, it seems likely that it is this polymerisation that confers the structural integrity required for sperm stability and motility.…”

Section: Reproductionmentioning

confidence: 99%

The importance of selenium to human health

2000

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“…In particular, its ability to directly reduce phospholipid hydroperoxides within biomembranes and lipoproteins makes GPx4 unique among antioxidative enzymes (Thomas et al, 1990;Sattler et al, 1994). Moreover, recent data suggest a role for GPx4 as a structural protein (Ursini et al, 1999) and as a regulator of apoptosis (Nomura et al, 1999), gene expression (BrigeliusFlohe, 2006) and eicosanoid biosynthesis (Weitzel and Wendel, 1993). Whether the catalytic activity of the enzyme is required for all these biological functions remains to be investigated.…”

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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Dual Function of the Selenoprotein PHGPx During Sperm Maturation

Cited by 811 publications

References 38 publications

A proteomic analysis on human sperm tail: comparison between normozoospermia and asthenozoospermia

A proteomic analysis on human sperm tail: comparison between normozoospermia and asthenozoospermia

The importance of selenium to human health

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

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