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Query: UNIPROT:P36969 (phospholipid hydroperoxide glutathione peroxidase)
 344 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Spermatozoa are highly sensitive to oxidative stress. The epididymis, a natural sperm reservoir, has maturational and storage functions. The epididymis may also protect spermatozoa from oxidative injury by elaborating scavengers of reactive oxygen species (ROS). Therefore, we have evaluated the mRNA expression of antioxidant enzymes in the normal rat epididymis and the effects of efferent duct ligation no the expression of these enzymes. Adult rat epididymides were harvested, divided into caput, corpus and cauda and processed for RNA extraction. Additional adult rats were subjected to unilateral efferent duct ligation and the epididymides harvested at 1, 4, 8, 16 or 28 days after the procedure. Antioxidant enzyme mRNA expression was assessed by Northern blot analysis using 32P-labelled DNA probes derived from known cDNA sequences for classical cellular glutathione peroxidase (GSHPx), phospholipid hydroperoxide glutathione peroxidase (PHGPX), secretory epididymal glutathione peroxidase (E-GPX), copper-zinc superoxide dismutase (SOD), secretory epididymal superoxide dismutase (E-SOD) and catalase. Specific mRNA levels were measured, with gene expression evaluated relative to total RNA, not per organ. Variations in lane loading were controlled by measuring the levels of 28S ribosomal RNA. GSHPx, PHGPX, SOD and catalase mRNA were detected in the caput, corpus and cauda epididymis. E-GPX mRNA was only detected in the caput, whereas E-SOD mRNA was primarily detected in the corpus. At 28 days after efferent duct ligation, epididymal weight decreased by 34% relative to controls (p < 0.05). With the exception of PHGPX, the relative mRNA levels of the antioxidant enzymes studied did not change after efferent duct ligation. This study demonstrates that mRNAs for multiple antioxidant enzymes are expressed in the epididymis and that the relative expression of these enzymes remains largely unchanged in response to efferent duct ligation. Taken together, these results suggest that antioxidant enzymes may play an important, region-specific role in epididymal function. Expression of the secretory antioxidant enzymes E-SOD and E-GPX is region-specific, indicating that the need for antioxidant enzymes may vary along the length of the epididymis.
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PMID:Identification and characterization of antioxidant enzyme mRNAs in the rat epididymis. 929 18

The selenoenzyme phospholipid hydroperoxide glutathione peroxidase (PHGPx, EC 1.11.1.12) is present, in both free and membrane-bound form, in several mammalian tissues. It utilizes thiols such as glutathione to specifically scavenge phospholipid hydroperoxides. The testis exhibits the highest PHGPx-specific activity so far measured, and interest in the presence and function of the enzyme in this tissue has recently grown. Here we report the localization of PHGPx in rat epididymal spermatozoa and its distribution in subfractions obtained by sucrose density gradient centrifugation. Immunochemical evidence and enzymatic activity revealed for the first time that PHGPx is present in sperm heads and tail midpiece mitochondria. The binding of the enzyme to spermatozoa, head, and mitochondria was barely affected by ionic strength or thiols or detergents, as compared to the detachment of PHGPx obtained from testis nuclei. Moreover, we demonstrated that pure PHGPx exhibits a higher thiol-oxidase activity toward isolated epididymal caput protamines than toward protamines from epididymal cauda. These results suggest a role for the enzyme in the maturation of spermatozoa through the metabolism of hydroperoxides and sperm thiol oxidation, in addition to its serving as an antioxidant protector.
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PMID:Distribution and possible novel role of phospholipid hydroperoxide glutathione peroxidase in rat epididymal spermatozoa. 940 61

Mammalian caput and cauda epididymidal spermatozoa exhibit diverse stages of maturation, and their plasma membrane shows diverse composition and stability levels, thus enabling these spermatozoa to undergo the acrosomal reaction after transit through the epididymis. As a result, the study of antiperoxidative mechanisms is quite relevant, since epididymal spermatozoa must be properly protected against agents such as reactive oxygen species, which can impair the complex maturation process. We considered activities of certain enzymes (glutathione peroxidase [GPx], phospholipid hydroperoxide glutathione peroxidase [PHGPx], glutathione reductase [GR], superoxide dismutase [SOD], and catalase [CAT]) and the vitamin E content in isolated rat caput and cauda epididymidal spermatozoa. The results indicate that caput epididymidal sperm have significantly greater PHGPx (3.5x), GPx (2.4x), and SOD (1.7x) activities, as well as a greater amount of vitamin E (3.8x). There were no detectable differences in the GR and CAT activities of caput and cauda epididymidal spermatozoa. The substantial drop in PHGPx activity during epididymal transit is discussed in relation to an additional function of this enzyme: the use of caput sperm protamines as a sulfhydryl substrate. In vitro peroxidation of the two sperm populations by the free radical generator (azo-initiator) 2,2'-azobis(2-amidinopropane) dihydrochloride revealed that only about 13% of the vitamin E content of the caput epididymidal spermatozoa was consumed, which contrasts with the greater consumption (about 70%) of the vitamin in cauda epididymidal spermatozoa. Selective inhibition of PHGPx, SOD, or CAT did not change this picture. The higher susceptibility of cauda epididymidal spermatozoa to radicals is discussed in relation to the diverse enzymatic activities, vitamin E content, and peroxidative response. These factors are correlated with the different stages of sperm cell maturation, which are characterized-from caput to cauda epididymidis-by progressive destabilization of the plasma and acrosomal membranes.
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PMID:Antioxidant systems in rat epididymal spermatozoa. 974 22

Selenium (Se) and selenoproteins such as glutathione peroxidases are necessary for the proper development and fertilizing capacity of sperm cells. Phospholipid hydroperoxide glutathione peroxidase (PHGPx, E.C. 1.11.1.12) is a monomeric seleno-enzyme present in different mammalian tissues in soluble and bound form. Its function, like the other glutathione peroxidases, was originally viewed as a protective role against hydroperoxides, but direct and indirect evidence indicates that it has additional regulatory roles. PHGPx is present in testis cells and sperm cells, and its appearance is hormone regulated. We present here biochemical data, which clearly indicate that the enzyme specific activity in rat is age-dependent during the life-span monitored (from 36 to 365 days), with a maximum at 3 months of age in the testis germ cells and at 6 months of age in the isolated epididymal sperm cells. Western blotting and immunocytochemical analysis by means of anti-PHGPx antibodies show the different distribution and the strong binding of PHGPx in the testes and sperm cell subcellular compartments (nucleus, acrosome, mitochondria and residual bodies) of rats of different age. The presence of the protein exhibits in the testis cells a pattern different from that of the catalytic activity, with a maximum at 6 months of age. The subcellular distribution of PHGPx is qualitatively, but not quantitatively, unchanged during ageing. These different behaviours are compared and discussed.
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PMID:Enzymatic and immunochemical evaluation of phospholipid hydroperoxide glutathione peroxidase (PHGPx) in testes and epididymal spermatozoa of rats of different ages. 1190 56

The protective effect of ginseng intestinal metabolite-I (GIM-I) against doxorubicin-induced testicular toxicity was investigated in 5-week-old ICR male mice. GIM-I was administered orally to mice at a dose of 50 mg/kg daily for 4 weeks. From the second week, doxorubicin was coadministered intraperitoneally to the animals at a dose of 3 mg/kg once a week for 3 weeks (a total of 9 mg/kg). The body weight, spermatogenic activities (Sertoli cell, repopulation, and epididymal indices), and serum levels of lactate dehydrogenase (LDH) and creatine phosphokinase (CPK) were significantly decreased by doxorubicin treatment (P<0.01), while the combined treatment of GIM-I with doxorubicin resulted in parameters similar to the control. In the testes of doxorubicin-treated animals, almost all of the germ cells disappeared and were replaced by fibrinoid debris in the seminiferous tubules. Germ cell injury was significantly attenuated by GIM-I coadministration. The mRNA for phospholipid hydroperoxide glutathione peroxidase (PHGPx), a testis-specific antioxidant, was greatly decreased by doxorubicin treatment, and less decreased with GIM-I coadministration. These findings indicate that GIM-I may be partially protective against doxorubicin-induced testicular toxicity.
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PMID:Ginseng intestinal metabolite-I (GIM-I) reduces doxorubicin toxicity in the mouse testis. 1212 3

Phospholipid hydroperoxide glutathione peroxidase (PHGPx, 20 kDa) and sperm nuclei glutathione peroxidase (snGPx, 34 kDa) are two selenoproteins present in mammalian testis and epididymal spermatozoa. They originate from the differential splicing of the PHGPx gene and appear to play important roles in sperm physiology. To determine the stages of spermatogenesis in which they are present, we compared the expression pattern of these two enzymes in highly purified populations of germ cells during specific phases of differentiation. In Northern and Western blotting experiments, both PHGPx transcript and protein were markedly expressed in pachytene spermatocytes and round spermatids. In contrast, the testis-specific snGPx was detected at both the mRNA and protein level only in haploid round spermatids. Accordingly, the developmental analysis of testicular RNAs from rats of different ages first revealed the appearance of PHGPx and snGPx transcripts at Day 20 and Day 30, respectively. Furthermore, both meiotic and postmeiotic cells contained catalytically active PHGPx/snGPx, with higher activity in the haploid cells. The intracellular distribution of PHGPx in mitochondria and nuclei of meiotic cells was demonstrated by immunocytochemical electron microscopy and Western blotting. These findings provide evidence that the PHGPx gene is differentially spliced during the meiotic prophase and haploid cell phases of spermatogenesis.
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PMID:Differential splicing of the phospholipid hydroperoxide glutathione peroxidase gene in diploid and haploid male germ cells in the rat. 1253 3

Sperm mitochondria undergo remodeling during posttesticular maturation that includes extensive disulfide cross-linking of proteins of the outer membrane to form the insoluble mitochondrial capsule. The relationship of these changes to mitochondrial function in mature gametes is unclear. The phospholipid hydroperoxide glutathione peroxidase (GPX4; also termed PHGPx) represents a major disulfide bond-stabilized protein of the mitochondrial capsule, and it is readily released by disulfide-reducing agents. However, in addition to GPX4, we detected a second major protein of 26 kDa (MP26) that was eluted from purified hamster sperm tails by the disulfide-reducing agent dithiothreitol. The objectives of the present study were to identify and characterize MP26 and to explore its potential role in mitochondrial function. Proteomic analysis of MP26 by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) identified 14 peptides with sequence identity to a member of the short-chain dehydrogenase/reductase superfamily termed P26h, which was implicated previously in hamster sperm-zona binding, and with high sequence similarity to mouse lung carbonyl reductase. Indirect immunofluorescence localized MP26 to the midpiece, and two-dimensional PAGE and immunoblot analysis identified a single MP26 isoform of pI 9.0. Immunoblot analyses of cauda epididymal fluid and of purified sperm plasma membranes and mitochondria revealed the exclusive localization of MP26 to the mitochondrial fraction. These data indicate that MP26 does not function in zona binding; instead, like GPX4, it may be associated with the mitochondrial capsule and play an important role in sperm mitochondrial function.
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PMID:Identification of a hamster sperm 26-kilodalton dehydrogenase/reductase that is exclusively localized to the mitochondria of the flagellum. 1668 46

Gopc (Golgi-associated PDZ- and coiled-coil motif-containing protein)(-/-) mice are infertile, showing globozoospermia, coiled tails, and a stratified mitochondrial sheath. Transmission electron microscope (TEM) images of the spermatozoa were studied quantitatively to analyze disorganization processes during epididymal passage. Factors maintaining straight tail and normal mitochondrial sheath were also studied by TEM and immunofluorescent microscopy. Sperm tails retained a normal appearance in the proximal caput epididymidis. Tail disorganization started between the proximal and the middle caput epididymidis, and the latter is the major site for it. The tail moved up through the defective posterior ring and coiled around the nucleus to various degrees. Tail coiling occurred in the caput epididymidis suggesting it was triggered by cytoplasmic droplet migration. SPATA19/spergen-1, a candidate mitochondrial adhesion protein, remained on the stratified mitochondria, while GPX4/PHGPx, a major element of the mitochondrial capsule, was unevenly distributed on them. From these findings, we speculate GPX4 is necessary to maintain normal sheath structure, and SPATA19 prevents dispersal of mitochondria, resulting in a stratified mitochondrial sheath formation in Gopc(-/-) spermatozoa. The epididymal epithelium was normal in structure and LRP8/apoER2 expression suggesting that tail abnormality is due to intrinsic sperm factors. Three cell structures are discussed as requisite factors for maintaining a straight tail during epididymal maturation: 1) a complete posterior ring to prevent invasion of the tail into the head compartment, 2) stable attachment of the connecting piece to the implantation fossa, and 3) a normal mitochondrial sheath supported by SPATA19 and supplied with sufficient and normally distributed GPX4.
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PMID:Factors maintaining normal sperm tail structure during epididymal maturation studied in Gopc-/- mice. 1736 Sep 59

Antioxidants in the male reproductive tract are the main defence factors against oxidative stress caused by reactive oxygen species production, which compromises sperm function and male fertility. This study was designed to determine the activity of antioxidant enzymes, such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), in the testicular and epididymidal tissues of adult male European bison (Bison bonasus). The reproductive tract tissues were subjected to real-time reverse transcriptase-polymerase chain reaction (RT-PCR) analysis to quantify mRNA expression levels of five antioxidant enzymes: copper/zinc SOD (Cu/Zn SOD), secretory extracellular SOD (Ec-SOD), CAT, phospholipid hydroperoxide glutathione peroxidase (PHGPx) and GPx5. The corpus and cauda epididymidal tissues displayed greater (p < 0.05) SOD activity compared with the testicular tissue. It was found that CAT activity was lowest (p < 0.05) in the cauda epididymidis, whereas negligible GPx activity was detected in the reproductive tract tissues. There were no detectable differences in the mRNA expression level of Cu/Zn SOD among the different reproductive tract tissues. Small amounts of Ec-SOD mRNA were found in the reproductive tract, particularly in the epididymides. The caput and cauda epididymides exhibited greater (p < 0.05) level of CAT mRNA expression, whereas PHGPx mRNA was more (p < 0.05) expressed in the testis. Furthermore, extremely large amounts of GPx5 mRNA were detected in the caput epididymidal tissue compared with other tissues of the reproductive tract. It can be suggested that the activity of the antioxidant enzymes and the relative gene expression of the enzymes confirm the presence of tissue-specific antioxidant defence systems in the bison reproductive tract, which are required for spermatogenesis, epididymal maturation and storage of spermatozoa.
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PMID:Antioxidant enzyme activity and mRNA expression in reproductive tract of adult male European Bison (Bison bonasus, Linnaeus 1758). 2245 32

Thiol groups of cysteine residues represent redox centers involved in multiple biological functions. It has been postulated that changes in the redox status of mammalian epididymal spermatozoa contribute to the sperm maturation process. The present work shows the thiol-disulfide protein profile of stallion epididymal spermatozoa achieved by two-dimension electrophoresis and MALDI-TOF/TOF mass spectrometry of proteins labeled with a thiol-reactive fluorescent tag, monobromobimane. Our results have shown the formation of disulfide bonds in several sperm protein fractions during the epididymal maturation process. The majority of the oxidized thiol sperm proteins identified correspond to structural molecules of the flagellum (as the outer dense fiber-1 protein - ODF1), followed by glycolytic enzymes (as glyceraldehyde-3-phosphate dehydrogenase spermatogenic), antioxidant protectors (as glutathione S-transferase and phospholipid hydroperoxide glutathione peroxidase - PHGPx). The magnitude of the thiol oxidation differs between proteins, and was more drastic in polypeptides with molecular weights of up to 33kDa, identified as ODF1 and PHGPx. A kinase anchor protein, a voltage-dependent anion channel protein and a zona pellucida-binding protein were also found in the polypeptide samples that contained oxidized SH groups. These proteins may be modified or controlled by the mechanisms involved in the cysteine-redox changes, corroborating the belief that a correct degree of protein oxidation is required for the stabilization of sperm structure, protection against oxidative damage, induction of progressive sperm motility and fertilization.
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PMID:Thiol-disulfide proteins of stallion epididymal spermatozoa. 2441 25


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