Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.6 (RNA polymerase)
 34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pausing of RNA polymerase II (Pol II) during early transcription, mediated by the negative elongation factor (NELF) complex, allows cells to coordinate and appropriately respond to signals by modulating the rate of transcriptional pause release. Promoter proximal enrichment of Pol II occurs at uterine genes relevant to reproductive biology; thus, we hypothesized that pausing might impact endometrial response by coordinating hormonal signals involved in establishing and maintaining pregnancy. We deleted the NELF-B subunit in the mouse uterus using PgrCre (NELF-B UtcKO). Resulting females were infertile. Uterine response to the initial decidual stimulus of NELF-B UtcKO was similar to that of control mice; however, subsequent full decidual response was not observed. Cultured NELF-B UtcKO stromal cells exhibited perturbances in extracellular matrix components and also expressed elevated levels of the decidual prolactin Prl8a2, as well as altered levels of transcripts encoding enzymes involved in prostaglandin synthesis and metabolism. Because endometrial stromal cell decidualization is also critical to human reproductive health and fertility, we used small interfering to suppress NELF-B or NELF-E subunits in cultured human endometrial stromal cells, which inhibited decidualization, as reflected by the impaired induction of decidual markers PRL and IGFBP1. Overall, our study indicates NELF-mediated pausing is essential to coordinate endometrial responses and that disruption impairs uterine decidual development during pregnancy.-Hewitt, S. C., Li, R., Adams, N., Winuthayanon, W., Hamilton, K. J., Donoghue, L. J., Lierz, S. L., Garcia, M., Lydon, J. P., DeMayo, F. J., Adelman, K., Korach, K. S. Negative elongation factor is essential for endometrial function.
 ...
PMID:Negative elongation factor is essential for endometrial function. 3033 1

Mitochondrial oxidative phosphorylation (OXPHOS) is essential for ATP production to maintain sperm linear motility during migration from the uterus to the oviduct. However, ROS are generated as by-products of OXPHOS, causing stress and damaging the sperm quality. This study aimed to clarify the ROS targets in sperm mitochondria that decrease linear motility and to investigate whether mitochondria-target antioxidants (PQQ and CoQ10) affect mitochondrial activity and sperm motility. Sperm linear motility pattern, ATP production, and mitochondrial activity were decreased with increasing ROS levels during incubation in the low-glucose medium. However, sperm motility patterns and ROS levels were not significantly changed in the high-glucose medium. Moreover, the gene expression system (mt-DNA, mitochondrial transcription factor-A (TFAM) and RNA polymerase (POLRMT)) in sperm mitochondria was damaged during incubation in the low-glucose medium. Interestingly, PQQ treatment increased the mt-DNA stability and decreased the damage to TFAM and POLRMT, which resulted in high expression of mitochondrial genes. Furthermore, the antioxidants increased mitochondrial activity and maintained sperm linear motility under the low glucose condition. These results revealed that both ATP production and the mitochondrial transcription system are damaged with increasing ROS levels in sperm that show a linear motility pattern. Treatment with antioxidants, such as PQQ and CoQ10, is beneficial tool to maintain sperm linear motility.
 ...
PMID:Negative effects of ROS generated during linear sperm motility on gene expression and ATP generation in boar sperm mitochondria. 3121 63


<< Previous 1 2 3 4 5 6 7