Kisspeptin receptor (KISS1R) signaling plays a critical role in the regulation of reproduction. We investigated the role of kisspeptin-stimulated KISS1R internalization, recycling, and degradation in the modulation of KISS1R signaling. Kisspeptin stimulation of Chinese hamster ovary or GT1-7 cells expressing KISS1R resulted in a biphasic increase in intracellular Ca(2+) ([Ca(2+)]i), with a rapid acute increase followed by a more sustained second phase. In contrast, stimulation of the TRH receptor, another Gq/11-coupled receptor, resulted in a much smaller second-phase [Ca(2+)]i response. The KISS1R-mediated second-phase [Ca(2+)]i response was abolished by removal of kisspeptin from cell culture medium. Notably, the second-phase [Ca(2+)]i response was also inhibited by dynasore, brefeldin A, and phenylarsine oxide, which inhibit receptor internalization and recycling, suggesting that KISS1R trafficking contributes to the sustained [Ca(2+)]i response. We further demonstrated that KISS1R undergoes dynamic ligand-dependent and -independent recycling. We next investigated the fate of the internalized kisspeptin-KISS1R complex. Most internalized kisspeptin was released extracellularly in degraded form within 1 hour, suggesting rapid processing of the internalized kisspeptin-KISS1R complex. Using a biotinylation assay, we demonstrated that degradation of cell surface KISS1R was much slower than that of the internalized ligand, suggesting dissociated processing of the internalized kisspeptin-KISS1R complex. Taken together, our results suggest that the sustained calcium response to kisspeptin is dependent on the continued presence of extracellular ligand and is the result of dynamic KISS1R trafficking.
Introduction: In development of cancer chronic inflammation plays a major role. Most established determinants of Prostate Carcinoma (PCa) are modern life style genetics, and age. In the first prostate biopsy, approximately 1 out 5 men i.e., 20% with PCa may be misdiagnosed. Therefore, there is clear requirement of novel markers, which can detect both clinically significant PCa, and prevent unnecessary biopsy. Some solid tumours found to have association of Neutrophil to Lymphocyte Ratio (NLR), Platelate to Lymphocyte Ratio (PLR) and Red-cell Distribution Width (RDW).Aim: Aim of this study was to scrutinise the significance of association of Prostate Specific Antigen (PSA), PLR, NLR and RDW with PCa. Materials and Methods: This study was conducted using the cross-sectional method in the Department of Pathology, Geetanjali Medical College and Hospital, Udaipur, Rajasthan between Jan 2018 to Nov 2020. In this cross-sectional study 84 patients who underwent Tran Rectal Ultrasound (TRUS) guided were included. Complete Blood Count (CBC) was used to determine PLR, NLR and RDW and biochemical test for PSA. Patients were divided into two groups; having benign and malignant pathology. Unpaired t-test, Mann-whitney U test, logistic regression analysis and correlation were performed for statistical analysis. Results: With the use of univariate logistic regression, association between PSA, NLR, PLR, RDW values and PCa detection was determined. We found that serum PSA was significantly more in the PCa group (as BPH and prostatitis are both benign conditions so are kept in nonPCa group) compared to other two groups (p<0.001). There was no statistically significant difference in NLR, PLR and RDW values (p=0.150, p=0.070. p=0.441, respectively was found in nonPCa and PCa group). Conclusion: PSA has statistically significant association with PCa group but PLR, NLR and RDW was not considered to be the significant predictor in benign as well as malignant group.
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