Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.25.1 (proteasome)
 28,817 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Localization of proteasomes in spermatozoa from patients with varicocele-associated sterility was studied by means of immunolabeling with the MPC21 monoclonal antibody detecting the C3 subunit of the 20S proteasome. The reaction was visualized for electron microscopy using the secondary Nano-Gold-coupled antibody with Gold-Enhancement in pre-embedding technique. We found that semen samples from varicocele patients contained a large amount of abnormal spermatozoa characterized by the presence of dispersed chromatin and large residual bodies (cytoplasmic droplets) as well as spermatids at various stages of spermiogenesis. In normal spermatozoa, the immunolabeling was found in the acrosome, postacrosomal regions, nuclear vacuoles, in the neck and in the middle-piece as well as in the residual bodies, while chromatin remained unlabeled. In varicocele spermatozoa, the immunolabeling was also associated with chromatin and large residual bodies (cytoplasmic droplets). In contrast to normal, mature spermatozoa, the chromatin of the cells at earlier stages of spermiogenesis was strongly immunolabeled. The association of proteasomes with sperm chromatin and large residual bodies can be the sign of abnormality and disturbances in spermatogenesis associated with varicocele.
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PMID:Proteasome localization and ultrastructure of spermatozoa from patients with varicocele--immunoelectron microscopic study. 1205 29

Assessment of sperm ubiquitination and DNA fragmentation as sperm functional markers are proposed to complement routine semen analysis. This study focuses on the evaluation of these markers in infertile men with varicocele or exposed to occupational background. The results were compared with normozoospermic men. Semen parameters in both groups were lower than those in the control group. Ubiquitination median, as a marker for functionality of the ubiquitin-proteasome system, was also lower in both groups. The ubiquitination median showed a significant positive correlation with motility in both groups, while it showed only a negative correlation with sperm morphology in the varicocele group. DNA fragmentation showed a significant correlation with semen parameters, in total varicocele and also total exposure groups. In conclusion, significant difference of sperm ubiquitination between normal and study groups further validates that sperm ubiquitination as a potential molecular marker for sperm evaluation in addition to routine semen analysis in clinical laboratories.
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PMID:Sperm ubiquitination and DNA fragmentation in men with occupational exposure and varicocele. 2359 55

Varicocele is a major cause of infertility and may impair spermatogenesis. This study evaluated the molecular consequences of varicocele on the induction of heat-shock proteins, intracellular chaperones involved in stress responses, and of the ubiquitin-proteasome system, which is participates in the removal of defective sperm in the testis and epididymis. Wistar rats were randomly divided into three groups: surgically induced left varicocele, sham-operated, and untreated controls. Two months after surgery, we observed significantly reduced sperm parameters, DNA integrity, and protamine content in the sperm retrieved from the left epididymis compared to the right epididymis in the varicocele group, as well as compared to sperm retrieved from the left epididymis of the sham and control groups. According to Western blot analysis, we observed significantly higher HSPA2 expression in testicular tissue from the left testis compared to the right testis in the varicocele group or the left testis of the control group. Immunohistochemical analysis showed that expression of HSPA2 was higher in the round spermatid and sperm from the left varicocele compared to the control group. There was normally less HSPA2 expressed in the caput and corpus compared to the cauda of the epididymis in the control group, but this pattern was altered in the caput epididymis of the varicocele group. Levels of ubiquitination were also remarkably lower in the left testis of the varicocele group. Therefore, varicocele impacts expression of HSPA2 and ubiquitination.
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PMID:Evaluation of heat-shock protein A2 (HSPA2) in male rats before and after varicocele induction. 2504 41

Sperm proteins undergo post-translational modifications, such as phosphorylation, acetylation, and ubiquitination, which in turn play a key role in determining their fertilizing ability. In the current study, we examined the sperm proteome of men with unilateral and bilateral varicocele to identify the key proteins affected by acetylation to gain an insight into the difference in the severity of affected sperm function in the latter. An LTQ-Orbitrap Elite hybrid mass spectrometer system was used to profile the sperm proteome in pooled unilateral and bilateral varicocele patients. Bioinformatics database and tools, such as UniProtKB, Ingenuity Pathway Analysis Software (IPA) and Metacore, were used to identify the differentially expressed proteins (DEPs) involved in the acetylation process. A total of 135 DEPs in the spermatozoa of unilateral and bilateral varicocele patients were found to be affected by acetylation. The majority of these DEPs found were regulated by key transcription factors such as androgen receptor, p53, and NRF2. Furthermore, the DEPs predicted to be affected by the acetylation process were associated with fertilization, acrosome reaction, mitochondrial dysfunction and oxidative stress. Aberrant expression of proteins and their differential acetylation process may affect the normal physiological functions of spermatozoa. Protein-protein interactions identified dysregulation of the proteasome complex in the bilateral varicocele group. Damage to the proteasome complex may result in aggregation of the misfolded proteins, which in turn increase sperm DNA damage and apoptosis in patients with bilateral varicocele.
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PMID:Functional Analysis of Differentially Expressed Acetylated Spermatozoal Proteins in Infertile Men with Unilateral and Bilateral Varicocele. 3236 53