title: Role of PTEN-Akt-CREB Signaling Pathway in Nervous System impairment of Rats with Chronic Arsenite Exposure.
abstract: The nervous system is a target of arsenic toxicity. Phosphatase and tensin homologue deleted on chromosome 10/protein kinase B/cAMP-response element binding protein (PTEN/Akt/CREB) signaling pathway has been reported to be involved in maintaining normal function of the nervous system, modulating growth and proliferation of neurocyte, regulating neuron synaptic plasticity, and long-term memory. And many studies have demonstrated that expressions of PTEN, Akt, and CREB protein were influenced by arsenic, but it is not clear whether this signaling pathway is involved in the nervous system impairment of rats induced by chronic arsenite exposure, and we have addressed this in this study. Eighty male Sprague-Dawley (SD) rats were randomly divided into eight groups (n = 10 each), four groups exposed to NaAsO2 (0, 5, 10, and 50 mg/L NaAsO2 in drinking water) for 3 months, the other four groups exposed to NaAsO2 (0, 5, 10, 50 mg/L NaAsO2 in drinking water) for 6 months. Hematoxylin and eosin (HE) staining showed that chronic arsenite exposure induced varying degrees of damage in cerebral neurons. And arsenite exposure increased arsenic amount in serum and brain samples in a dose- and time-dependent manner. Moreover, the protein levels of PTEN and Akt in brain tissue were not significantly changed compared with the control group, but p-Akt, CREB, and p-CREB were all significantly downregulated in arsenite-exposed groups with a dose-dependent pattern. These results suggested that chronic arsenite exposure negatively regulated the PTEN-Akt-CREB signaling pathway, and dysfunction of the signaling pathway might be one of the mechanisms of nervous system impairment induced by chronic arsenite exposure.
authors: Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Key Lab of Etiologic Epidemiology of Ministry of Health and Education Bureau of Heilongjiang Province(23618504), Harbin Medical University, 157 Baojian Road, Harbin, 150081, China.
authors: Lisha
authors: L
authors: Qu
authors: Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Key Lab of Etiologic Epidemiology of Ministry of Health and Education Bureau of Heilongjiang Province(23618504), Harbin Medical University, 157 Baojian Road, Harbin, 150081, China.
authors: Yanhui
authors: Y
authors: Gao
authors: Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Key Lab of Etiologic Epidemiology of Ministry of Health and Education Bureau of Heilongjiang Province(23618504), Harbin Medical University, 157 Baojian Road, Harbin, 150081, China.
authors: Hongna
authors: H
authors: Sun
authors: Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Key Lab of Etiologic Epidemiology of Ministry of Health and Education Bureau of Heilongjiang Province(23618504), Harbin Medical University, 157 Baojian Road, Harbin, 150081, China.
authors: Hui
authors: H
authors: Wang
authors: Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Key Lab of Etiologic Epidemiology of Ministry of Health and Education Bureau of Heilongjiang Province(23618504), Harbin Medical University, 157 Baojian Road, Harbin, 150081, China.
authors: Xiaona
authors: X
authors: Liu
authors: Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Key Lab of Etiologic Epidemiology of Ministry of Health and Education Bureau of Heilongjiang Province(23618504), Harbin Medical University, 157 Baojian Road, Harbin, 150081, China. hrbmusdj@163.com.
authors: Dianjun
authors: D
authors: Sun
mesh_terms: D000818:Animals; D018053:Arsenites / Q000633:toxicity*; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D050882:CREB-Binding Protein / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D008297:Male; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D018053:Arsenites; D050882:CREB-Binding Protein; C494365:Crebbp protein, rat; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C487216:Pten protein, rat; C015001:arsenite
keywords: Arsenic; Phosphatase and tensin homologue deleted on chromosome 10 (PTEN); Protein kinase B (Akt); Signaling pathway; cAMP-response element binding protein(CREB)