Mouse Anti Human Ras-related C3 Botulinum Toxin Substrate 1 Hybridoma [DQUD-SBD2-2]

Chloroquine (CQ) is an antimalarial drug widely used in rheumatic, immunological and infectious diseases. CQ is also a well-known autophagy inhibitor. It slows the progression of renal injury in patients with rheumatology diseases. Long-term CQ treatment could also damage podocytes which are highly differentiated cells wrapping the glomerular capillary to maintain renal filtration. However, the related underlying mechanism remains unclear. The effects of CQ treatment on podocytes need to be elucidated. Our results showed that CQ diminished cell motility and disrupted actin cytoskeleton in human podocytes in vitro. Totally 210 up-regulated and 67 down-regulated differentially expressed proteins (DEPs) were identified after CQ treatment in podocytes by using tandem mass tag (TMT)-labeled quantitative proteomics analysis. Gene Ontology (GO) analysis revealed that proteins mainly functioned in cell motility, cell adhesion, localization of cells and response to external stimulus. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment showed that DEPs were predominantly associated with lysosome, cell adhesion molecules (CAMs) and cytokine-cytokine receptor interaction. Protein-protein interaction (PPI) analysis revealed that syndecan-4 was the core protein in regulating podocyte adhesion among differentially expressed CAMs. Moreover, activated RhoA, Cdc42 and Rac1 decreased after CQ treatment. Taken together, our findings suggested that CQ could alter the stability of podocyte cytoskeleton. Proteomic analysis revealed important molecules for understanding the effects of CQ on human podocytes.

Background: Ras-related C3 botulinum substrate 1 (Rac1) is a member of the small molecule family Rho guanosine triphosphate (GTP)ases. Recent findings reveal epigenetic downregulation of Rac1 is a mechanism of depression. Aims: The purpose of this study was to evaluate Rac1 as a therapeutic target for depression we examine the association between thiopurines, which inhibit Rac1, and the risk of depression among US veterans. Methods: This study uses data spanning January 2000-May 2019, comparing thiopurine exposure (no exposure, less than one year, 1-2.9 years, 3-5 years, and greater than five years) in two separate cohorts, a rheumatoid arthritis cohort and inflammatory bowel disease cohort. We estimate the hazard of depression using a time dependent cox proportional hazards model. Results: A total of 76,763 rheumatoid arthritis and 46,787 inflammatory bowel disease patients met all inclusion criteria. Patients exposed to thiopurines less than one year have a 27% (hazard ratio=1.272; 95% confidence interval=(1.038-1.559)) and 67% (hazard ratio=1.667 95% confidence interval=(1.501-1.850)) higher risk of depression in the rheumatoid arthritis and inflammatory bowel disease cohorts, respectively. In the inflammatory bowel disease cohort, we find the risk of depression is increased for up to five years of thiopurine exposure. Conclusion: These results provide evidence that Rac1 regulation is a viable therapeutic target for depression. Further research into therapeutics targeting Rac1 for the treatment of depression is warranted.