Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P56851 (epididymal)
 11,273 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Macrophage migration inhibitory factor (MIF) has been rediscovered as a proinflammatory cytokine, pituitary hormone, and glucocorticoid-induced immunoregulator. A survey of tissue distribution revealed that MIF expression is not limited to T lymphocytes, but exists in several other tissues; however, its presence in adipose tissue has never been investigated. In this study, we examined the expression of MIF in adipose tissue using the rat epididymal fat pad and murine 3T3-L1 adipocytes. Northern and Western blot analyses revealed the expression of MIF mRNA and MIF protein, respectively, in both the fat pad and the adipocyte cell line. In immunohistochemistry, a positive staining reaction with an anti-rat MIF antibody was detected largely in the cytosol of adipocytes of the epididymal fat pad. To examine the production and release of MIF by adipocytes, we examined its content in the culture medium of the 3T3-L1 adipocytes. The results showed that MIF content was 1.6 +/- 0.48 ng/ml (mean +/- SD) after 24 hr culture, and the content was increased up to 9.7 +/- 2.8 ng/ml by stimulation with TNF-alpha (50 nM). Since TNF-alpha produced in adipocytes is known to induce insulin resistance, the results suggest the possibility that MIF plays an important role in the mechanism of insulin resistance often observed in obesity and diabetes via regulation of TNF-alpha expression.
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PMID:Identification of macrophage migration inhibitory factor in adipose tissue and its induction by tumor necrosis factor-alpha. 919 42

During the epididymal transit, mammalian spermatozoa acquire new surface proteins necessary for male gamete function. We have previously shown that membranous vesicles, called epididymosomes, interact with spermatozoa allowing the transfer of some proteins to sperm surface within the epididymal lumen. The protein composition of those vesicles has been investigated to document the mechanisms of protein transfer from epididymosomes to spermatozoa. Electrophoretic analysis revealed that protein composition is different from the epididymal soluble compartment as well as from similar vesicles present in the semen. Protein association with epididymosome is very strong as revealed by resistance to extraction with detergent. Matrix-assisted laser desorption ionization time-of-flight as well as immunodetection techniques have been used to identify some proteins associated to epididymosomes and spermatozoa. An aldose reductase known for its 20alpha-hydroxysteroid dehydrogenase activity and the cytokine (macrophage migration inhibitory factor) have been identified. These two proteins have been immunolocalized in principal cells of the epididymal epithelium, a more intense signal being detected in the distal epididymal segment as well as in the vas deferens. Database search revealed that these two proteins are characterized by the lack of a signal peptide. These results are discussed with regard to a possible apocrine mode of secretion of these proteins acquired by spermatozoa during the epididymal transit.
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PMID:Aldose reductase and macrophage migration inhibitory factor are associated with epididymosomes and spermatozoa in the bovine epididymis. 1282 72

The function of macrophage migration inhibitory factor (MIF) in sperm maturation was studied by investigating its role in the biochemical maturation of the outer dense fibres. Rat sperm obtained from the caput and cauda epididymis were stimulated overnight with either recombinant MIF or MIF-containing vesicles originating from epididymal fluid at various concentrations. The zinc content of both the sperm and the medium was determined by means of atomic absorption spectrometry. Incubation in both recombinant MIF and vesicular MIF resulted in a statistically significant decrease of the zinc content in stimulated caput sperm of approximately 50%. In parallel, the conditioned media showed a clear increase in the concentration of this trace metal. The effect of MIF was less marked in cauda sperm. In addition, we demonstrated a statistically significant increase of detectable free thiol groups in the sperm mid- and principle piece in isolated rat sperm after stimulation with MIF at concentrations of 25 and 50 ng/ml. Our data suggest that MIF plays an important role in the maturation process of rat sperm during epididymal transit by inducing the elimination of zinc and affecting the amount of free sulphydryl groups in the sperm flagella.
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PMID:Influence of macrophage migration inhibitory factor (MIF) on the zinc content and redox state of protein-bound sulphydryl groups in rat sperm: indications for a new role of MIF in sperm maturation. 1516 22

The present study examines whether and to what extent the profiles of adipose-derived factors are altered in epididymal and subcutaneous adipose tissues of long-term fasted/refed and of fasted rats treated by recombinant leptin. Fasting was characterized by three successive metabolic phases. Minor differences in the time-course and magnitude of response were detected between the two adipose sites. Leptin, adiponectin, resistin, adiponutrin, and insulin-like growth factor-1 (IGF-1) gene expressions differentially decreased according to the fasting duration. mRNA levels reached a minimum in late fasting for these secreted factors, being decreased by 60-90% for adiponectin, resistin, and IGF-1, 95-98% for leptin and by 100% for adiponutrin. Refeeding partially or totally restored their mRNA expression in epididymal adipose. Expression levels of apolipoprotein E (ApoE), angiotensinogen (AGT), adipsin and macrophage migration inhibitory factor (MIF) were either unchanged or slightly affected. In leptin-treated rats, leptin mRNA concentrations were significantly decreased in phase 2 of fasting (by 85%) from levels in control phosphate-buffered saline (PBS)-treated rats in both tissues. Leptin treatment also decreased resistin mRNA levels (by 78% in P2L and 63% in P3L relative to control groups) in subcutaneous adipose. These data suggest that adiponectin, resistin, adiponutrin, and IGF-1 could be involved in overall energy homeostasis during prolonged fasting, as leptin is. The mechanisms that underlie the expressions of these adipose-secreted factors remain to be determined.
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PMID:Differences in mRNA expression of adipocyte-derived factors in response to fasting, refeeding and leptin. 1523 24

Even tough differentiated spermatozoa are unable of transcriptional or translational activity; the sperm surface undergoes major modifications in macromolecules composition during the transit along the male reproductive tract. This is the result of sequential, well orchestrated interactions between the male reproductive tract secretions and the transiting male gamete. This is particularly true when spermatozoa transit along the epididymis. The epididymis is a long convoluted tubules in which the spermatozoa leaving the testis have to transit. The unraveled epididymal tubule can be as long as 80 m in stallion, and the transit time of spermatozoa is of 3-12 days depending on the species. The epididymis is usually divided in three segments: the caput (proximal part), the corpus, and cauda. While the cauda epididymides acts as a sperm reservoir, the caput and corpus are responsible for sperm maturation. This means that, under androgen control, the epididymal epithelium secretes proteins that will interact sequentially with sperm surface. Some of the sperm proteins acquired during maturation along the excurrent duct behave as integral membrane proteins. In fact, some epididymal originating proteins are glycosylphosphatidylinositol (GPI)-anchored to the sperm plasma membrane. Our laboratory has shown that some of these proteins are secreted in an apocrine manner by the epididymal epithelium and are associated to exosomes, called epididymosomes. Epididymosomes are rich in sphingomyelin and are characterized by a high cholesterol/phospholipids ratio. Many proteins are associated to epididymosomes, some of which are selectively transferred to spermatozoa during the epididymal transit. We have identified some of these exosomes associated proteins transferred to the maturing spermatozoa. These include two enzymes involved in the polyol pathway: an aldose reductase and a sorbitol dehydrogenase. A cytokine named MIF (macrophage migration inhibitory factor) is another protein associated to exosomes who is transferred to spermatozoa during the epididymal transit. We hypothesized that both the polyol pathway and MIF secreted in an apocrine fashion by the epididymal epithelium modulate sperm motility during the transit along the male reproductive tract. Finally, P25b, belonging to a family of sperm surface proteins (P26h/P34H) necessary for the binding to the surface of the egg, is also acquired through the interaction between epididymosomes and the male gamete. In vitro studies have defined the conditions of protein transfer when epididymal spermatozoa are co-incubated with epididymosomes. The transfer of selected proteins to specific membrane domains of spermatozoa is saturable, temperature and pH-dependent, being optimal at pH 6.5. The presence of zinc in the incubation medium, but not of calcium neither magnesium, significantly increases the efficiency of protein transfer. These results show that exosomes play a role in sperm epididymal maturation which is an essential event to produce male gametes with optimal fertilizing ability.
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PMID:Role of exosomes in sperm maturation during the transit along the male reproductive tract. 1589 44

During epididymal transit, mammalian spermatozoa acquire new proteins involved in the acquisition of motility and of male gamete fertilising ability. We have previously shown that membranous vesicles called epididymosomes are involved in the transfer of epididymal-originating proteins to spermatozoa. The cytokine macrophage migration inhibitory factor (MIF) is one of these proteins but the role played by MIF in relation to epididymal sperm maturation still remains unclear. As this protein has already been shown to bear different functions depending on its location, we investigated its distribution along the epididymis and in different compartments of human semen. Northern and Western blot analysis as well as immunohistochemical studies show that MIF is expressed all along the epididymis with a higher level of transcript in the proximal segment. MIF is associated with two types of membranous vesicles, i.e. epididymosomes and prostasomes, the latter being prostate-originating membranous vesicles present in the semen. In semen, MIF is associated with spermatozoa, prostasomes as well as the soluble fraction. The amount of MIF in the seminal fluid varies from one individual to another but does not correlate with the amount of MIF associated with ejaculated spermatozoa. There is a negative correlation between the amount of sperm-associated MIF and the percentage of motility in different semen samples. Sperm separation using discontinuous Percoll gradient centrifugation shows a higher amount of MIF associated with poorly motile spermatozoa compared to highly motile spermatozoa present in the lower Percoll fraction. These results are discussed with regards to the possible involvement of MIF in sperm motility acquisition during the epididymal transit.
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PMID:Macrophage migration inhibitory factor in the human epididymis and semen. 1605 83

Originally defined as a lymphokine inhibiting the random migration of macrophages, the macrophage migration inhibitory factor (MIF) is an important mediator of the host response to infection. Beyond its function as a classical cytokine, MIF is currently portrayed as a multifunctional protein with growth-regulating properties present in organ systems beyond immune cells. In previous studies, we detected substantial amounts of MIF in the rat epididymis and epididymal spermatozoa, where it appears to play a role during post-testicular sperm maturation and the acquisition of fertilization ability. To explore its presence in other species not yet examined in this respect, we extended the range of studies to the bull. Using a polyclonal antibody raised against MIF purified from bovine eye lenses, we detected MIF in the epithelium of the adult bovine epididymis with the basal cells representing a prominently stained cell type. A distinct accumulation of MIF at the apical cell pole of the epithelial cells and in membranous vesicles localized in the lumen of the epididymal duct was obvious. In the fetal bovine epididymis, we also detected MIF in the epithelium, whereas MIF accumulation was evident at the apical cell surface and in apical protrusions. By immunoelectron microscopy of the adult bovine epididymis, we localized MIF in apical protrusions of the epithelial cells and in luminal membrane-bound vesicles that were found in close proximity to sperm cells. Although the precise origin of the MIF-containing vesicles remains to be delineated, our morphological observations support the hypothesis that they become detached from the apical surface of the epididymal epithelial cells. Additionally, an association of MIF with the outer dense fibers of luminal spermatozoa was demonstrated. Data obtained in this study suggest MIF release by an apocrine secretion mode in the bovine epididymis. Furthermore, MIF localized in the basal cells of the epithelium and in the connective tissue could be responsible for regulating the migration of macrophages in order to avoid contact of immune cells with spermatozoa that carry a wide range of potent antigens.
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PMID:Immunohistochemical detection of macrophage migration inhibitory factor in fetal and adult bovine epididymis: release by the apocrine secretion mode? 1665 26

During epididymal transit, spermatozoa acquire new proteins. Some of these newly acquired proteins behave as integral membrane proteins, including glycosylphosphatidylinositol (GPI)-anchored proteins. This suggests that the secreted epididymal proteins are transferred to spermatozoa by an unusual mechanism. Within the epididymal lumen, spermatozoa interact with small membranous vesicles named epididymosomes. Many proteins are associated with epididymosomes and the protein composition of these vesicles varies along the excurrent duct and differs from soluble intraluminal proteins. Some epididymosome-associated proteins have been identified and their functions in sperm maturation hypothesized. These include P25b, a zona pellucida binding protein, macrophage migration inhibitory factor, enzymes of the polyol pathway, HE5/CD52, type 5 glutathione peroxidase, and SPAM1 or PH-20. The electrophoretic patterns of proteins associated to epididymosomes are complex and some of these proteins are transferred to defined surface domains of epididymal spermatozoa. Epididymosomes collected from different epididymal segments interact differently with spermatozoa. This protein transfer from epididymosomes to spermatozoa is time-dependent, temperature-dependent and pH-dependent, and is more efficient in the presence of zinc. Some proteins are segregated to lipid raft domains of epididymosomes and are selectively transferred to raft domains of the sperm plasma membrane. Some evidence is presented showing that epididymosomes are secreted in an apocrine manner by the epididymal epithelial cells. In conclusion, epididymosomes are small membranous vesicles secreted in an apocrine manner in the intraluminal compartment of the epididymis and play a major role in the acquisition of new proteins by the maturing spermatozoa.
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PMID:Epididymosomes are involved in the acquisition of new sperm proteins during epididymal transit. 1758 85

Epididymosomes are small membranous vesicles secreted by epithelial cells within the luminal compartment of the epididymis. In bovine, many proteins are associated with epididymosomes, and some of them, such as the glycosylphosphatidylinositol (GPI)-anchored protein P25b, macrophage migration inhibitory factor (MIF), and aldose reductase (AKR1B1), are transferred to spermatozoa during the epididymal maturation process. P25b is associated with detergent-resistant membrane (DRM) domains of epididymal spermatozoa, whereas MIF and AKR1B1 are cytosolic proteins associated with detergent-soluble fractions. In this study, we tested the hypothesis that DRM domains are also present in the epididymosomes and that P25b DRM-associated proteins in these vesicles are transferred to the DRMs of spermatozoa. The presence of DRMs in epididymosomes was confirmed by their insolubility in cold Triton X-100 and their low buoyant density in sucrose gradient. Furthermore, DRMs isolated from epididymosomes are characterized by the exclusive presence of ganglioside GM1 and by high levels of cholesterol and sphingomyelin. Biochemical analysis indicated that P25b is linked to DRM in epididymosomes, whereas MIF and AKR1B1 are completely excluded from these membrane domains. Proteolytic treatment of epididymosomes and immunoblotting studies showed that P25b is affected by trypsin or pronase proteolysis. In contrast, MIF and AKR1B1 are not degraded by proteases, suggesting that they are localized within epididymosomes. Interaction studies between epididymosomes and epididymal spermatozoa demonstrated that P25b is transferred from the DRM of epididymosomes to the DRM of the caput epididymal spermatozoa as a GPI-anchored protein. Together, these data suggest that specific localization and compartmentalization of proteins in the epididymosomes coordinate the association of epididymal proteins with the different functional structures of spermatozoa.
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PMID:Compartmentalization of proteins in epididymosomes coordinates the association of epididymal proteins with the different functional structures of bovine spermatozoa. 1916 73

Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine and has been implicated in inflammatory diseases. However, little is known about the regulation of MIF in adipose tissue and its impact on wound healing. The aim of this study was to investigate MIF expression in inflamed adipose and determine its role in inflammatory cell recruitment and wound healing. Adipose tissue was harvested from subcutaneous adipose tissue layers of 24 healthy subjects and from adipose tissue adjacent to acutely inflamed wounds of 21 patients undergoing wound debridement. MIF protein and mRNA expression were measured by ELISA and RT-PCR. Cell-specific MIF expression was visualized by immunohistochemistry. The functional role of MIF in cell recruitment was investigated by a chemotaxis assay and by flow cytometry of labeled macrophages that were injected into Mif-/-and wildtype mice. Wound healing was evaluated by an in vitro scratch assay on human fibroblast monolayers. MIF protein levels of native adipose tissue and supernatants from acutely inflamed wounds were significantly elevated when compared to healthy controls. MIF mRNA expression was increased in acutely inflamed adipose tissue indicating the activation of MIF gene transcription in response to adipose tissue inflammation. MIF is expressed in mature adipocytes and in infiltrated macrophages. Peripheral blood mononuclear cell migration was significantly increased towards supernatants derived from inflamed adipose tissue. This effect was partially abrogated by MIF-neutralizing antibodies. Moreover, when compared to wildtype mice, Mif-/-mice showed reduced infiltration of labeled macrophages into LPS-stimulated epididymal fat pads in vivo. Finally, MIF antibodies partially neutralized the detrimental effect of MIF on fibroblast wound healing. Our results indicate that increased MIF expression and rapid activation of the MIF gene in fat tissue adjacent to acute wound healing disorders may play a role in cell recruitment to the site of inflammation and wound healing.
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PMID:Macrophage Migration Inhibitory Factor in Acute Adipose Tissue Inflammation. 2634 53


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