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Chemokine Receptor Expression and Regulatory Mechanisms
Published in Thomas R. O’Brien, Chemokine Receptors and AIDS, 2019
Ricardo M. Richardson, Ralph Snyderman, Bodduluri Haribabu
A newly described family of proteins, known as regulators of G-protein signaling (RGS), reduces the strength of G-protein signaling by enhancing its GTPase activity thus making less Gβy available (82, 83). Regulation of RGS activity could, therefore, play a role in chemoattractant receptor cross-desensitization by affecting signal strength. In this regard, transient overexpression of RGS1, RGS3 and RGS4, but not RGS2, was found to inhibit chemoattractant receptor-mediated motility in a transfected lymphoid cell line (84). In our studies, expression of RGS4 in RBL-2H3 inhibited phosphoinositide hydrolysis and intracellular Ca2+ mobilization to PAFR, but not to fMLPR or CXCR1 (85). In contrast, expression of RGS 1 blocked fMLPR-, but not PAFR-mediated Ca2+ mobilization (85). These findings lend evidence to the notion that groups of receptors may be regulated separately by specific subtypes of RGS.
Applications of imaging genomics beyond oncology
Published in Ruijiang Li, Lei Xing, Sandy Napel, Daniel L. Rubin, Radiomics and Radiogenomics, 2019
Xiaohui Yao, Jingwen Yan, Li Shen
Genetic factors were found to play a major role in the etiology of schizophrenia. A meta-analysis using pooled data from 12 twin studies estimated the heritability of schizophrenia to be approximately 80% [107]. To date, around 30 schizophrenia-associated loci have been identified through GWAS to play a role in conferring the risk of schizophrenia, such as catechol-O-methyltransferase (COMT), Disrupted In Schizophrenia 1 (DISC1), regulator of G protein signaling 4 (RGS4), neuregulin 1 (NRG1), dystrobrevin binding protein 1 (DTNBP1), D-amino acid oxidase activator (DAOA), phosphodiesterase 4B (PDE4B), Dopamine- and cAMP-regulated phosphoprotein, Mr 32 kDa (DARPP-32) protein phosphatase 1 regulatory subunit 3B and glutamate metabotropic receptor 3 (GRM3) [108]. There are also growing evidences from exome sequencing studies indicating that some risk genes and pathways are affected by both common and rare variants [109], which implies large effects of rare variants on individual risk. This can be best exemplified by 11 large, rare recurrent CNVs and loss-of-function variants in set domain containing 1A, histone lysine methyltransferase (SETD1A) [109,110]. Evidences from other exome sequencing studies imply more other rare variants conferring substantial individual risk [111,112]. Despite the remarkable progress in the search for risk genes associated with schizophrenia, translation of genetic associations into targetable mechanisms related to disease pathogenesis remains poorly understood.
100 MCQs from Dr. David Browne and Colleagues
Published in David Browne, Selena Morgan Pillay, Guy Molyneaux, Brenda Wright, Bangaru Raju, Ijaz Hussein, Mohamed Ali Ahmed, Michael Reilly, MCQs for the New MRCPsych Paper A, 2017
Dr Karen Fleming, Dr Michael Kenewali, Dr Manas Sarkar, Dr Daniel White
Much work has been done to identify susceptibility genes in schizophrenia and bipolar disorder. The current evidence implicates specific genes in both disorders. Evidence supports neuregulin 1 (NGR1), dysbindin (DTNBP1), DISC1, D-amino acid oxidase activator (DAOA (G72)), D-amino acid oxidase (DAO) and regulator of G-protein signalling (RGS4) as schizophrenia susceptibility loci. For bipolar disorder the strongest evidence supports DAOA (G72) and brain-derived neurotrophic factor (BDNF). Increasing evidence suggests an overlap in genetic susceptibility across the traditional classification system that dichotomised psychotic disorders into schizophrenia or bipolar disorder, most notably with association findings at DAOA (G72), DISC1, and NGR1. (1, p 572)
RGS7 silence protects palmitic acid-induced pancreatic β-cell injury by inactivating the chemokine signaling pathway
Published in Autoimmunity, 2023
Yurong Zhu, Jun Li, Tao Ba, Yuan Sun, Xiangyun Chang
The analysis of GEO dataset GSE118230 showed the level of R7 family members (Figure 1A). The top three members of the expression level are RGS4, RGS2, and RGS7 (Figure 1A). The role of RGS4 and RGS2 in pancreatic β-cells has been reported previously [24–27]. Thus, RGS7 was selected for subsequent study. GEO dataset GSE118230 showed that the expression level of RGS7 was significantly increased after 7 days of treatment with PA (Figure 1B). Then, total of four pancreatic β-cell lines (Beta-TC-6, NIT-1, Min6, and HIT-T15) were employed to measure RGS7 expression. As shown in Figure 1C,D, RGS7 expression was the highest in Beta-TC-6 cells and the lowest in Min6 cells. Therefore, Beta-TC-6 and Min6 cells were selected for our study. We then treated the pancreatic β-cells Beta-TC-6 and Min6 cells, and measured the change of RGS7 expression. The results showed that the levels of RGS7 mRNA and protein in PA group were obviously upregulated compared with control group (Figure 1E,F). These results suggested that RGS7 might play a vital role in PA-induced pancreatic β-cells.
Emerging therapeutic targets for cardiac hypertrophy
Published in Expert Opinion on Therapeutic Targets, 2022
Alexander J. Winkle, Drew M. Nassal, Rebecca Shaheen, Evelyn Thomas, Shivangi Mohta, Daniel Gratz, Seth H. Weinberg, Thomas J. Hund
Additional studies, however, have shown similar success blocking hypertrophy, but not without detrimental effect. An overexpression model of the GTPase-activating protein RGS4 resulted in a reduction of hypertrophy with a corresponding increase in mortality [102]. Brancaccio et al. have demonstrated the crucial role melusin – a protein involved in load sensing – plays in maintaining cardiac function during hypertrophic conditions [103]. Interestingly, given the previously discussed use of calcineurin inhibitors to safely prevent hypertrophy, a separate study focusing on a separate, endogenous inhibitor Zaki-4β found a similar inhibition of hypertrophy, but significantly reduced function as evaluated by two parameters of LV diastolic function [104].