Molecular cloning and characterization of the epididymis-specific glutathione peroxidase-like protein secreted in the porcine epididymal fluid

Okamura, Nobuyuki; Iwaki, Yoshinobu; Hiramoto, Shinsuke; Tamba, Michiko; Bannai, Shiro; Sugita, Yoshiki; Syntin, Patrick; Dacheux, Françoise; Dacheux, Jean‐Louis

doi:10.1016/s0304-4165(97)00016-0

Cited by 49 publications

(31 citation statements)

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“…Most of the major proteins identified in the cauda epididymidis of eutherian mammals are enzymes (such as glycosidases, including mannosidase, hexosaminidase, galactosidase), peroxidases (GPX5) or binding proteins (PGDS, clusterin, lactoferrin and HE1/NCP2) (Kirchhoff et al 1996;Okamura et al 1997;Fouchécourt et al 2002). These epididymal proteins have not been identified in the platypus, and the major epididymal proteins in the platypus (PXN-FBPL, SPARC and E-OR20) have never been identified in the epididymis of any other mammal.…”

Section: Discussionmentioning

confidence: 99%

New proteins identified in epididymal fluid from the platypus (Ornithorhynchus anatinus)

Dacheux

Labas

et al. 2009

Reprod. Fertil. Dev.

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The platypus epididymal proteome is being studied because epididymal proteins are essential for male fertility in mammals and it is considered that knowledge of the epididymal proteome in an early mammal would be informative in assessing the convergence and divergence of proteins that are important in the function of the mammalian epididymis. Few of the epididymal proteins that have been identified in eutherian mammals were found in platypus caudal epididymal fluid, and the major epididymal proteins in the platypus (PXN-FBPL, SPARC and E-OR20) have never been identified in the epididymis of any other mammal. Abstract. The platypus epididymal proteome is being studied because epididymal proteins are essential for male fertility in mammals and it is considered that knowledge of the epididymal proteome in an early mammal would be informative in assessing the convergence and divergence of proteins that are important in the function of the mammalian epididymis. Few of the epididymal proteins that have been identified in eutherian mammals were found in platypus caudal epididymal fluid, and the major epididymal proteins in the platypus (PXN-FBPL, SPARC and E-OR20) have never been identified in the epididymis of any other mammal.

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Section: Discussionmentioning

confidence: 99%

New proteins identified in epididymal fluid from the platypus (Ornithorhynchus anatinus)

Dacheux

Labas

et al. 2009

Reprod. Fertil. Dev.

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“…Sperm are particularly vulnerable to increased levels of reactive oxygen species (ROS) as their membranes contain a high content of polyunsaturated fatty acids that are extremely sensitive to peroxidative damage (Aitken et al, 1993;Storey, 1997). As sperm themselves possess only low levels of cytoplasmic antioxidants, having shed most of their cytoplasm, they are reliant for protection on antioxidant scavengers, synthesized and secreted by the epididymal epithelial cells, including extracellular superoxide dismutase (Williams et al, 1998a,b) and an unusual isoform of glutathione peroxidase, GPX5 (Ghyselinck et al, 1990;Perry et al, 1992;Lefrancois et al, 1993;Okamura et al, 1997;Vernet et al, 1997;Williams et al, 1998a,b).…”

Section: Introductionmentioning

confidence: 99%

“…GPX5 is an unusual member of the mammalian GPX family, as, unlike the well-known mammalian GPXs 1-4 (Brigelius-Flohe, 1999), it does not contain a selenocysteine (SeCys) at its active site, having instead a cysteine residue (Perry et al, 1992); it is thus termed a selenium (Se)-independent GPX. GPX5 is expressed exclusively by the caput epididymis (Ghyselinck et al, 1990;Perry et al, 1992;Lefrancois et al, 1993;Williams et al, 1998a,b) and associates with sperm during transit (Okamura et al, 1997;Vernet et al, 1997;Williams et al, 1998a,b), specifically with the plasma membrane overlying the acrosome, which is particularly sensitive to peroxidative damage (Jones and Mann, 1977). It has therefore been postulated that GPX5 protects sperm from peroxide-mediated attack (Perry et al, 1992;Williams et al, 1998a,b).…”

Section: Introductionmentioning

confidence: 99%

“…Although an attractive hypothesis, the function of GPX5 as an active glutathione peroxidase has been questioned (Rocher et al, 1992;Okamura et al, 1997) as the SeCys at the active site of the four major mammalian glutathione peroxidase isozymes was thought essential for activity; the higher nucleophilicity and lower pK of Se compared with sulphur make for a more reactive redox centre. However, Se-independent GPXs from organisms outside the mammalian class exhibit catalytic activity (Herbette et al, 2007) and play a highly significant and physiological role in antioxidant defense as phospholipid hydroperoxidases (Beeor-Tzahar et al, 1995;Tang et al, 1995Tang et al, , 1996Faltin et al, 1998;Tripp et al, 1998;Avery and Avery, 2001;Herbette et al, 2002;Gaber et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

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Epididymal specific, selenium-independent GPX5 protects cells from oxidative stress-induced lipid peroxidation and DNA mutation

Taylor¹,

Robson²,

Houghton³

et al. 2013

Human Reproduction

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study qustion: Can selenium (Se) independent, epididymal-specific glutathione peroxidase 5 (GPX5) protect CHO-K1 cells from oxidative damage and, more specifically, from lipid peroxidation and DNA mutation?summary answer: CHO-K1 cells expressing GPX5 have increased resistance to oxidative challenge and, more specifically, decreased levels of lipid peroxidation and decreased levels of the downstream DNA lesion 8-oxo-7,8-dihydroguanine (8-oxodG) what is known already: GPX5 associates with sperm during transit of the epididymis, and has been postulated to protect sperm from peroxide-mediated attack. However, its function as an active glutathione peroxidase has been questioned due to substitution of the classical selenocysteine residue at its active site. Indirect evidence for a functional role for GPX5 has been provided by in vivo studies, in particular from the GPX5 knockout mouse whereby offspring sired by GPX5 2/2 males have a higher rate of spontaneous abortion and developmental defects, attributed to increased oxidative injury (8-oxodG) to sperm DNA, but only when the GPX5 2/2 males are over 1 year of age. Interestingly, we have previously shown severely reduced levels of GPX5 in humans.study design, size, duration: To look more directly at its role in protection against oxidative damage, we have used an in vitro system, generating a CHO-K1 mammalian cell line expressing recombinant rat GPX5.participants/materials, setting, methods: We have used the recombinant CHO-K1 cells to determine whether GPX5 is able to protect these cells from an administered oxidative challenge, using a range of approaches. We compared the viability of GPX5-expressing cells with control cells by both MTT and trypan blue exclusion assays. We next investigated whether GPX5 protects the cells specifically from lipid peroxidation, by using the fluorescent reporter molecule C11-BODIPY (581/591) , and thus from downstream DNA mutation, by comparing levels of the DNA lesion 8-oxodG. We also investigated whether GPX5 can be transferred to rat sperm via epididymosomes.main results and the role of chance: GPX5-expressing CHO-K1 cells had increased viability compared with control cells following oxidative challenge (P , 0.005). We also found that GPX5-expressing CHO-K1 cells had significantly lower levels of C11-BODIPY (581/591) oxidation, and hence lipid peroxidation, compared with control cells. Levels of 8-oxodG DNA damage were also markedly lower in the nuclei of GPX5-expressing cells than in control cells. Finally, we showed that GPX5 can be transferred to rat sperm via epididymosomes.limitations, reasons for caution: GPX5 is not active in glutathione peroxidase assays using H 2 O 2 as the substrate. However, the related non-mammalian Se-independent GPXs show preference for electron donors other than glutathione, with a number utilizing thioredoxin as a reducing equivalent. Hence, the in vitro activity of GPX5 needs to be assessed using a range of alternative substrates and electron donors. GPX5 is secreted by the epididymis and associate...

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“…GPX5 секрети-руется в лумен эпидидимиса, связывается с го-ловками сперматозоидов и предотвращает их повреждение гидропероксидами. Возможно, GPX5 предотвращает преждевременную реак-цию акросом сперматозоидов во время их хра-нения в хвосте придатка яичка [5,8].…”

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Significance of glutathione peroxidases in endometrium function: facts, hypotheses, and research perspectives

2017

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Enzymes of glutathione peroxidase (GPX) family, together with peroxiredoxins, form thiol peroxidase superfamily, the property of which is the thiol-dependent catalysis of the hydroperoxide reduction. This property determines them as antioxidant protectors. Among human GPXs the eight forms are known, five of which are selenium-dependent (GPX1,2,3,4, and 6). The most number of facts supporting the substantial role of GPX in functioning of endometrium are linked with the GPX3, which is the secretory GPX. The number of candidate progesterone response elements in the promoter of GPX3 gene prevails over the number of candidate estrogen response elements; GPX3 is upregulated gene during postovulatory phase of reproductive cycle and during pregnancy; in the endometrial stroma, the transcription of Gpx3 is stimulated through the transcription factor HIF1α. Using laboratory animals, the spatial and temporal coincidence of Gpx3 activation and blastocyst implantation was observed. It was confirmed that GPX3 decreases hydrogen peroxide concentration in endometrium in pregnant animals and during in vitro decidualization. The vulnerability of reproductive function to physiological stress at the insufficient expression of GPX3 is hypothesized. The GPX3 enzymatic activity in endometrium is poorly investigated. The has been hypothesized that selenium-containing medications are effective in the endometrium receptivity improvement and in the supporting the normal embryo development (especially during the influence of physiological stressors) by the maintenance of the posttranscriptional, selenium-dependent stage of GPX3 biosynthesis in endometrium. Probably, the GPX3 expression can be increased by the steriods with gestagenic activity (through the increase of Gpx3 transcription, analogously to effect of progesterone). In contrast with the «classic» GPX (GPX1) and probably with most of other members of GPX family, GPX3 has a wide thiol specificity. It is proposed to assess the activity of GPX3 using the reduced homocysteine and cysteine as thiol substrates instead of the reduced glutathione.

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Molecular cloning and characterization of the epididymis-specific glutathione peroxidase-like protein secreted in the porcine epididymal fluid

Cited by 49 publications

References 22 publications

New proteins identified in epididymal fluid from the platypus (Ornithorhynchus anatinus)

New proteins identified in epididymal fluid from the platypus (Ornithorhynchus anatinus)

Epididymal specific, selenium-independent GPX5 protects cells from oxidative stress-induced lipid peroxidation and DNA mutation

Significance of glutathione peroxidases in endometrium function: facts, hypotheses, and research perspectives

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