title: Regulator of G protein signaling-1 modulates paraquat-induced oxidative stress and longevity via the insulin like signaling pathway in Caenorhabditis elegans.
abstract: Insulin or insulin like signaling (IIS) pathway is a crucial pathway in Caenorhabditis elegans associated with mediating longevity, and stress resistance. Regulators of G protein signaling (RGS) also modulate stress resistance and longevity in multiple in vitro and in vivo models. However, the mechanism underlying RGS mediating stress resistance and longevity remains largely unclear. Here we report that rgs-1, an important member of rgs family, is a novel modulator of IIS pathway in C. elegans. We found that the loss of rgs-1 dramatically promoted paraquat resistance in C. elegans. Further genetic analyses demonstrated that rgs-1 acted downstream of daf-2 and upstream of age-1, pdk-1, daf-16. Instead of affecting those IIS-associated genes in transcriptional process, loss of rgs-1 promoted DAF-16's nucleus translocation and subset genes' expression in paraquat-induced oxidative status. By this way, rgs-1 mutant worms exhibited lower ROS damage and longer survival time than wild type worms when both exposed to paraquat. Other than paraquat exposure, rgs-1 mutant also promoted lifespan and cadmium resistance relying on daf-16. As rgs is evolutionarily conserved, our findings open a new insight into rgs family and its role in paraquat-induced oxidative stress and longevity in C. elegans or even mammals.
authors.affiliation: Center for Nephrology and Metabolomics, Division of Nephrology and Rheumatology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
authors.forename: Mingyu
authors.initials: M
authors.lastname: Wu
authors.affiliation: Center for Nephrology and Metabolomics, Division of Nephrology and Rheumatology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Kang
authors.affiliation: Center for Nephrology and Metabolomics, Division of Nephrology and Rheumatology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Center for Nephrology and Metabolomics, Division of Nephrology and Rheumatology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
authors.forename: Chunyu
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Center for Nephrology and Metabolomics, Division of Nephrology and Rheumatology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China; Department of Biomedical Engineering, University of Houston, Houston, TX 77204, USA. Electronic address: cmohan@Central.UH.EDU.
authors.forename: Chandra
authors.initials: C
authors.lastname: Mohan
authors.affiliation: Center for Nephrology and Metabolomics, Division of Nephrology and Rheumatology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China. Electronic address: pengai@tongji.edu.cn.
authors.forename: Ai
authors.initials: A
authors.lastname: Peng
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D008136:Longevity / Q000187:drug effects* / Q000235:genetics; D009154:Mutation; D018384:Oxidative Stress / Q000187:drug effects* / Q000235:genetics; D010269:Paraquat / Q000633:toxicity*; D015398:Signal Transduction; D013002:Somatomedins / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; D051858:Forkhead Transcription Factors; D047908:Intracellular Signaling Peptides and Proteins; C000621048:Rgs-1 protein, C elegans; D013002:Somatomedins; C108831:daf-16 protein, C elegans; D010269:Paraquat
keywords: Insulin signaling; Longevity; Oxidative stress; Paraquat; rgs-1