title: Molecular control of arsenite-induced apoptosis in Caenorhabditis elegans: roles of insulin-like growth factor-1 signaling pathway.
abstract: Apoptosis is one of the main cellular processes in responses to arsenic, the well known environmental carcinogen. By using the nematode Caenorhabditis elegans as an in vivo model, we found that insulin-like growth factor-1 networks and their target protein DAF-16/FOXO, known as key regulators of energy metabolism and growth, played important roles in arsenite-induced apoptosis. Inactivation of DAF-2, AGE-1 and AKT-1 caused worms more susceptible to arsenite-induced apoptosis, which could be attenuated by DAF-16 knockout. Worms with inactivated AKT-2 and SGK-1 or with constitutively activated PDK-1 and AKT-1 showed low levels of apoptosis, which could be elevated by DAF-16 mutation. Our results demonstrated that DAF-2/IGF-1R, AGE-1/PI3K, PDK-1/PDK1 and AKT-1/PKB negatively regulated the arsenite-induced apoptosis, whereas AKT-2 and SGK-1 acted proapoptotically. DAF-16/FOXO antagonized IGF-1 signals in signaling the arsenite-induced apoptosis, and apoptosis promoted by DAF-16 inactivation was attributed to its higher sensitivity to oxidative stress.
authors.affiliation: Department of Life Science, Huainan Normal University, Huainan 232001, China. Electronic address: scwangl@hotmail.com.
authors.forename: Shunchang
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Life Science, Huainan Normal University, Huainan 232001, China; School of Life Sciences, Anhui University, Hefei 230601, China.
authors.forename: Xiaoxue
authors.initials: X
authors.lastname: Teng
authors.affiliation: Department of Life Science, Huainan Normal University, Huainan 232001, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Chemistry, University of Science & Technology of China, Hefei 230026, China.
authors.forename: Han-Qing
authors.initials: HQ
authors.lastname: Yu
authors.affiliation: Department of Life Science, Huainan Normal University, Huainan 232001, China; Key Laboratory of Ion Beam Bioengineering, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China.
authors.forename: Xun
authors.initials: X
authors.lastname: Luo
authors.affiliation: Key Laboratory of Ion Beam Bioengineering, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China.
authors.forename: An
authors.initials: A
authors.lastname: Xu
authors.affiliation: Key Laboratory of Ion Beam Bioengineering, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Wu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D018053:Arsenites / Q000633:toxicity*; D017173:Caenorhabditis elegans / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D004785:Environmental Pollutants / Q000633:toxicity*; D051858:Forkhead Transcription Factors; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D009154:Mutation; D018384:Oxidative Stress / Q000187:drug effects; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D018053:Arsenites; D029742:Caenorhabditis elegans Proteins; D004785:Environmental Pollutants; D051858:Forkhead Transcription Factors; D014157:Transcription Factors; C108831:daf-16 protein, C elegans; D007334:Insulin-Like Growth Factor I; D019869:Phosphatidylinositol 3-Kinases; C015001:arsenite
keywords: Apoptosis; Arsenite; Caenorhabditis elegans; FOXO; Insulin-like growth factor-1; Oxidative stress