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Differential Expression of Genes: DISCUSSION(5)

DISCUSSION(5)

Alzheimer disease has been linked to the aberrant transcription of the ubiquitin-B (UB-B) gene, caused by a +1 frame-shift during transcription. This misreading results in the translation of the dysfunctional UB-B +1 protein with the elongated C-terminus not capable of ligation to a substrate protein. Consequently, the amyloid protein within neurons is not properly ubiquitinated and degraded by proteasomes, causing the formation of amyloid plaques in Alzheimer disease-affected brain tissue. Intriguingly, the UB-B+1 frame shift product has been found in the aging human epididymis.

In segment analysis, the reduction in 20S core subunit expression was most significant in the corpus epididymis, which is in good agreement with our immunohistochemical data showing that proteasome-rich, endocytotic clear cells are particularly abundant within this epididymal segment. Clear cells have been implicated in the removal of intraluminal debris, derived from the breakdown of rejected sperm cytoplasmic droplets. The mechanism of epididymal sperm maturation and disposal of defective spermatozoa is not completely understood and may involve defective sperm marking by the UPP as well as the coating of defective spermatozoa by a procoagulatory glycoprotein, HEP64/fgl2.

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Differential Expression of Genes: DISCUSSION(9)

While we found that both constitutive p subunits and their inducible counterparts were expressed in the testis and epididymis, only the constitutional subunits showed significant expression changes in the tissues of the exposed animals. Products of two of the three examined UPP enzyme genes not directly associated with the proteasome, … Continue reading

Differential Expression of Genes: DISCUSSION(8)

However, several other genes showed significant expression level changes in certain segments alone after either THP or DNB exposure. This indicates that THP and DNB cause significant changes in gene expression in specific compartments of the male reproductive system. For example, Psmb8 showed a P-value of 0.156 between the control … Continue reading

Differential Expression of Genes: DISCUSSION(7)

Inducible proteasomal core subunits PSMB9, PMSB8, and PSMB10 replace their constitutive counterparts PMSB5, PMSB1, and PMSB2 in the professional antigen-presenting cells but are also present in other cell types, such as eye lens cells and the sperm acrosome. The expression of inducible subunit Pmsb8 as measured by semiquantitative RT was … Continue reading

Differential Expression of Genes: DISCUSSION(6)

We have shown that defective spermatozoa become ubiquitinated in the caput epididymis, presumably by the enzymatic ubiquitination machinery residing within epididymal fluid. The percentage of defective spermatozoa is reduced after passage through the corpus epididymis. Since proteasomes have also been detected in the epididymal fluid, it is possible that defective … Continue reading

Differential Expression of Genes: DISCUSSION(5)

Alzheimer disease has been linked to the aberrant transcription of the ubiquitin-B (UB-B) gene, caused by a +1 frame-shift during transcription. This misreading results in the translation of the dysfunctional UB-B +1 protein with the elongated C-terminus not capable of ligation to a substrate protein. Consequently, the amyloid protein within … Continue reading