ArticleProceedings of the National Academy of Sciences of the United States of America2015
Regulator of G protein signaling 6 is a critical mediator of both reward-related behavioral and pathological responses to alcohol.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.
- Identification of shared genetic architecture between non-alcoholic fatty liver disease and type 2 diabetes: A genome-wide analysis.Frontiers in endocrinology · 2023Pooled it
- Identification of Gβ5 Interactome Associated with Neuronal Development in Neuro-2a Cells through miniTurbo Proximity Labeling.ACS omega · 2026Article
- Advances in drug addiction research usingFrontiers in cell and developmental biology · 2026Review
- Parkinson Disease -Targeted Nanocapsules for Synergistic Treatment: Combining Dopamine Replacement and Neuroinflammation Mitigation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Regulator of G protein signaling 6 (RGS6) in dopamine neurons promotes EtOH seeking, behavioral reward, and susceptibility to relapse.Psychopharmacology · 2024Article
- A splice acceptor variant in RGS6 associated with intellectual disability, microcephaly, and cataracts disproportionately promotes expression of a subset of RGS6 isoforms.Journal of human genetics · 2024Article
- RGS6 drives cardiomyocyte death following nucleolar stress by suppressing Nucleolin/miRNA-21.Journal of translational medicine · 2024Article
- Regulator of G protein signaling protein 6 alleviates acute lung injury by inhibiting inflammation and promoting cell self-renewal in mice.Cellular & molecular biology letters · 2023Article
- RGS6 negatively regulates inhibitory G protein signaling in dopamine neurons and positively regulates binge-like alcohol consumption in mice.British journal of pharmacology · 2023Article
- RGS6 suppresses TGF-β-induced epithelial-mesenchymal transition in non-small cell lung cancers via a novel mechanism dependent on its interaction with SMAD4.Cell death & disease · 2022Article
- Hepatic Regulator of G Protein Signaling 6 (RGS6) drives non-alcoholic fatty liver disease by promoting oxidative stress and ATM-dependent cell death.Redox biology · 2021Article
- RGS14 Regulation of Post-Synaptic Signaling and Spine Plasticity in Brain.International journal of molecular sciences · 2021Review
- G protein-coupled receptors as potential targets for nonalcoholic fatty liver disease treatment.World journal of gastroenterology · 2021Review
- RGS Proteins as Critical Regulators of Motor Function and Their Implications in Parkinson's Disease.Molecular pharmacology · 2020Review
- Genome-wide association study for circulating fibroblast growth factor 21 and 23.Scientific reports · 2020Article
- Dopamine D2 autoreceptor interactome: Targeting the receptor complex as a strategy for treatment of substance use disorder.Pharmacology & therapeutics · 2020Review
- The sockeye salmon genome, transcriptome, and analyses identifying population defining regions of the genome.PloS one · 2020Article
- Regulator of G-protein signaling (RGS) proteins as drug targets: Progress and future potentials.The Journal of biological chemistry · 2019Review
- Age-dependent nigral dopaminergic neurodegeneration and α-synuclein accumulation in RGS6-deficient mice.JCI insight · 2019Article
- Regulator of G Protein Signaling 6 Facilities Cardiac Hypertrophy by Activating Apoptosis Signal-Regulating Kinase 1-P38/c-JUN N-Terminal Kinase 1/2 Signaling.Journal of the American Heart Association · 2018Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Alcohol is the most commonly abused drug worldwide, and chronic alcohol consumption is a major etiological factor in the development of multiple pathological sequelae, including alcoholic cardiomyopathy and hepatic cirrhosis. Here, we identify regulator of G protein signaling 6 (RGS6) as a critical regulator of both alcohol-seeking behaviors and the associated cardiac and hepatic morbidities through two mechanistically divergent signaling actions. RGS6(-/-) mice consume less alcohol when given free access and are less susceptible to alcohol-induced reward and withdrawal. Antagonism of GABA(B) receptors or dopamine D2 receptors partially reversed the reduction in alcohol consumption in RGS6(-/-) animals. Strikingly, dopamine transporter inhibition completely restored alcohol seeking in mice lacking RGS6. RGS6 deficiency was associated with alterations in the expression of genes controlling dopamine (DA) homeostasis and a reduction in DA levels in the striatum. Taken together, these data implicate RGS6 as an essential regulator of DA bioavailability. RGS6 deficiency also provided dramatic protection against cardiac hypertrophy and fibrosis, hepatic steatosis, and gastrointestinal barrier dysfunction and endotoxemia when mice were forced to consume alcohol. Although RGS proteins canonically function as G-protein regulators, RGS6-dependent, alcohol-mediated toxicity in the heart, liver, and gastrointestinal tract involves the ability of RGS6 to promote reactive oxygen species-dependent apoptosis, an action independent of its G-protein regulatory capacity. We propose that inhibition of RGS6 might represent a viable means to reduce alcohol cravings and withdrawal in human patients, while simultaneously protecting the heart and liver from further damage upon relapse.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.