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

The distribution of transglutaminase immunoreactivity in the male genital system of the rat has been studied at the light and electron microscopic levels using a highly specific polyclonal antibody. The antibody is obviously secreted in an apocrine fashion in the dorsal prostate as well as the coagulating gland. This moiety is responsible for semen clotting. In addition to the secretory moiety, epididymal sperm contain endogenous immunoreactive material in the cytoplasmic droplet. Whether this is added to the sperm within the epididymis--as is the immunoreactive material on the sperm head--or already present in developing sperm has to be elucidated by further immunoelectron microscopic studies.
 ...
PMID:Transglutaminase immunoreactivity in the male genital tract of the rat. 198 41

There is evidence that the mammalian female genital tract is capable of responding immunologically when challenged with alloantigens. The antigenic properties of male gametes have been well delineated. However, it is only rarely that a female mammal ever responds immunologically to the male gametic antigens as a result of coitus. When a proposed mechanism of suppression of antigenicity of epididymal spermatozoa was tested experimentally, the results indicated that two proteins (uteroglobin and transglutaminase) present in the prostate may be responsible for suppressing sperm antigenicity in the rabbit.
 ...
PMID:Suppression of epididymal sperm antigenicity in the rabbit by uteroglobin and transglutaminase in vitro. 613 Jun 1

Uteroglobin, a progesterone induced, pregnancy related protein, can be incorporated into higher molecular weight proteins by human placental Factor XIIIa. This process is time dependent, requires CaCl2 and can be inhibited by the addition of polylysine, dansylcadavarine or histamine. Crosslinking of uteroglobin into higher molecular weight proteins can also be brought about by guinea pig liver transglutaminase. Such a process may be involved in the modification of epididymal spermatozoa to suppress their antigenicity.
 ...
PMID:Crosslinking of uteroglobin by transglutaminase. 614 14

Two transglutaminase-mediated modifications of the rat epididymal spermatozoon surface were demonstrated in vitro. Transglutaminase was effective in promoting the binding of spermidine to the sperm. Moreover, the enzyme, by reacting with one of the major proteins secreted by the rat seminal vesicle epithelium, produced a modified form of the protein with a higher molecular weight and the capability of binding to the sperm cells. A specific physiological role for the enzyme, bringing about modifications of the rat sperm surface in the seminal fluid environment, is suggested.
 ...
PMID:Transglutaminase-mediated modifications of the rat sperm surface in vitro. 614 19

The pretreatment of epididymal spermatozoa with SV-IV, one of the major secretory protein produced by the epithelium of adult rat seminal vesicles, was found to markedly decrease their ability to induce in vivo peritoneal macrophage activation, measured as class II major histocompatibility complex surface antigen expression, superoxide anion production, phagocytic activity, and antigen presentation. In addition, the treatment of spermatozoa with SV-IV produced a significant decrease of their immunogenicity evaluated in vitro by [3H]thymidine incorporation in splenocyte/spermatozoon co-culture. The concurrent presence of SV-IV and transglutaminase, an enzyme secreted in large amounts from the rat anterior prostate, amplified these phenomena. The suppression of the epididymal sperm immunogenicity is suggested to be of crucial importance for the prevention of the immune response to the sperm introduced in the immunocompetent female genital tract during coitus.
 ...
PMID:Suppression of rat epididymal sperm immunogenicity by a seminal vesicle secretory protein and transglutaminase both in vivo and in vitro. 790 54

The immunosuppressive, anti-inflammatory and anti-thrombotic properties of SV-IV, a major protein secreted from the epithelium of rat seminal vesicles, were investigated after transglutaminase-catalyzed covalent incorporation of two molecules of spermidine (Spd) into the protein at the level of Gln-9 and Gln-86. The modified molecular form of the protein (Spd2-SV-IV) showed a more marked inhibitory activity on Con A-induced lymphocyte blastogenesis in comparison with the native protein, whereas no differences in the ability to inhibit the mixed lymphocyte reaction and to decrease the rat epididymal sperm immunogenicity were found between modified and native SV-IV. Spd2-SV-IV was also less effective than native SV-IV to inhibit platelet aggregation induced in vivo by different thrombogenic agents. In contrast, superimposable inhibitory tracings were observed in the in vitro platelet aggregation experiments performed with the two different molecular forms on the protein. Finally, Spd2-SV-IV was shown to retain unchanged the anti-inflammatory activity of native SV-IV.
 ...
PMID:Biological activities of a major protein secreted from the rat seminal vesicles after structural modification catalyzed by transglutaminase in vitro. 809 70

The epididymal lumen represents a unique extracellular environment because of the active sperm maturation process that takes place within its confines. Although much focus has been placed on the interaction of epididymal secretory proteins with spermatozoa in the lumen, very little is known regarding how the complex epididymal milieu as a whole is maintained, including mechanisms to prevent or control proteins that may not stay in their native folded state following secretion. Because some misfolded proteins can form cytotoxic aggregate structures known as amyloid, it is likely that control/surveillance mechanisms exist within the epididymis to protect against this process and allow sperm maturation to occur. To study protein aggregation and to identify extracellular quality control mechanisms in the epididymis, we used the cystatin family of cysteine protease inhibitors, including cystatin-related epididymal spermatogenic and cystatin C as molecular models because both proteins have inherent properties to aggregate and form amyloid. In this chapter, we present a brief summary of protein aggregation by the amyloid pathway based on what is known from other organ systems and describe quality control mechanisms that exist intracellularly to control protein misfolding and aggregation. We then present a summary of our studies of cystatin-related epididymal spermatogenic (CRES) oligomerization within the epididymal lumen, including studies suggesting that transglutaminase cross-linking may be one mechanism of extracellular quality control within the epididymis.
 ...
PMID:Extracellular quality control in the epididymis. 1758 87

CRES (cystatin-related epididymal spermatogenic), a member of the cystatin superfamily of cysteine protease inhibitors, is expressed in the epididymis and spermatozoa, suggesting specialized roles in reproduction. Several cystatin family members oligomerize, including cystatin C that forms amyloid deposits associated with cerebral amyloid angiopathy. Our studies demonstrate that CRES also forms oligomers. Size exclusion chromatography revealed the presence of multiple forms of CRES in the epididymal luminal fluid, including SDS-sensitive and SDS-resistant high molecular mass complexes. In vitro experiments demonstrated that CRES is a substrate for transglutaminase and that an endogenous transglutaminase activity in the epididymal lumen catalyzed the formation of SDS-resistant CRES complexes. The use of a conformation-dependent antibody that recognizes only the oligomeric precursors to amyloid, negative stain electron microscopy, and Congo Red staining showed that CRES adopted similar oligomeric and fibrillar structures during its aggregation as other amyloidogenic proteins, suggesting that CRES has the potential to form amyloid in the epididymal lumen. The addition of transglutaminase, however, prevented the formation of CRES oligomers recognized by the conformation antibody by cross-linking CRES into an amorphous structure. We propose that transglutaminase activity in the epididymal lumen may function as a mechanism of extracellular quality control by diverting proteins such as CRES from the amyloidogenic pathway.
 ...
PMID:Oligomerization and transglutaminase cross-linking of the cystatin CRES in the mouse epididymal lumen: potential mechanism of extracellular quality control. 1785 42