title: Intestinal Insulin Signaling Encodes Two Different Molecular Mechanisms for the Shortened Longevity Induced by Graphene Oxide in Caenorhabditis elegans.
abstract: Graphene oxide (GO) has been shown to cause multiple toxicities in various organisms. However, the underlying molecular mechanisms for GO-induced shortened longevity are still unclear. We employed Caenorhabditis elegans to investigate the possible involvement of insulin signaling pathway in the control of GO toxicity and its underlying molecular mechanisms. Mutation of daf-2, age-1, akt-1, or akt-2 gene induced a resistant property of nematodes to GO toxicity, while mutation of daf-16 gene led to a susceptible property of nematodes to GO toxicity, suggesting that GO may dysregulate the functions of DAF-2/IGF-1 receptor, AGE-1, AKT-1 and AKT-2-mediated kinase cascade, and DAF-16/FOXO transcription factor. Genetic interaction analysis suggested the involvement of signaling cascade of DAF-2-AGE-1-AKT-1/2-DAF-16 in the control of GO toxicity on longevity. Moreover, intestinal RNA interference (RNAi) analysis demonstrated that GO reduced longevity by affecting the functions of signaling cascade of DAF-2-AGE-1-AKT-1/2-DAF-16 in the intestine. DAF-16 could also regulate GO toxicity on longevity by functioning upstream of SOD-3, which encodes an antioxidation system that prevents the accumulation of oxidative stress. Therefore, intestinal insulin signaling may encode two different molecular mechanisms responsible for the GO toxicity in inducing the shortened longevity. Our results highlight the key role of insulin signaling pathway in the control of GO toxicity in organisms.
authors.affiliation: Key Laboratory of Environmental Medicine Engineering in Ministry of Education, Medical School, Southeast University, Nanjing 210009, China.|Department of Preventive Medicine, Bengbu Medical College, Bengbu 233020, China.
authors.forename: Yunli
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Environmental Medicine Engineering in Ministry of Education, Medical School, Southeast University, Nanjing 210009, China.|College of Life Sciences, Nanjing Agricultural University, Nanjing 210095, China.
authors.forename: Ruilong
authors.initials: R
authors.lastname: Yang
authors.affiliation: College of Life Sciences, Nanjing Agricultural University, Nanjing 210095, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Rui
authors.affiliation: Key Laboratory of Environmental Medicine Engineering in Ministry of Education, Medical School, Southeast University, Nanjing 210009, China.
authors.forename: Dayong
authors.initials: D
authors.lastname: Wang
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics*; D051858:Forkhead Transcription Factors / Q000235:genetics; D006108:Graphite / Q000633:toxicity*; D007328:Insulin / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism; D008136:Longevity / Q000187:drug effects*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics; D011972:Receptor, Insulin / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D029742:Caenorhabditis elegans Proteins; D051858:Forkhead Transcription Factors; D007328:Insulin; C108831:daf-16 protein, C elegans; D006108:Graphite; D019869:Phosphatidylinositol 3-Kinases; C100662:AGE-1 protein, C elegans; C107483:DAF-2 protein, C elegans; D011972:Receptor, Insulin; D051057:Proto-Oncogene Proteins c-akt; C494915:akt-1 protein, C elegans; C494916:akt-2 protein, C elegans