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.

RETRACTED ARTICLE:Bone mesenchymal stem cell-derived exosomal microRNA-29b-3p prevents hypoxic-ischemic injury in rat brain by activating the PTEN-mediated Akt signaling pathway

“…The gene for phosphatase and tensin homolog (PETN), which is located on human chromosome 19, encodes a dual phosphatase enzyme that dephosphorylates both protein and lipid substrates [16]. Also, PTEN is a negative regulator of the phosphatidylinositol 3-kinase/protein kinase B (PI3K/ Akt) signaling pathway [17], which is implicated in hypoxicischemic injury [18]. However, it has been unclear whether bone marrow mesenchymal stem cells (BMSCs)-derived exosomes and miR-29b-3p moderate the severity of ischemic brain injury and whether their regulation is dependent on PTEN or the Akt signaling pathway.…”

Impairments of spatial learning and memory following intrahippocampal injection in rats of 3-mercaptopropionic acid-modified CdTe quantum dots and molecular mechanisms

“…Some studies have suggested that toxins, such as propofol and arsenic, could impair basal synaptic transmission, hippocampal LTP, and memory, along with decreased p-Akt levels. 32,33 Our results showed that p-Akt was significantly downregulated in 3.5 nm MPA-modified CdTe QD exposure, which indicated that dysfunction of the PI3K-Akt signaling pathway might be one of the mechanisms of CNS impairment induced by MPA-modified CdTe QD exposure. However, the effects of 3.5 nm MPA-modified CdTe QDs on the phosphorylation of Akt are complicated in view of the findings that the mRNA level of the gene PIK3R5 (encoding PI3K) was significantly upregulated in high-dose 3.5 nm MPA-modified CdTe QD exposure, and decreased p-Akt levels were not dose-dependent.…”

Sodium Arsenite-Induced Learning and Memory Impairment Is Associated with Endoplasmic Reticulum Stress-Mediated Apoptosis in Rat Hippocampus

“…Three groups received 5, 10, 50 mg/L sodium arsenite for six consecutive months, and the other three groups received 5, 10, 50 mg/L sodium arsenite for 3 months and then received distilled water for another 3 months (Figure 1 ). Our pilot study provided an appropriate drug for this study (Zhang et al, 2013 ; Qu et al, 2016 ). All rat experiments were in strict accordance with the Chinese legislation on the use and care of laboratory animals and were approved by the University committees for animal experiments.…”

“…Next, the membranes were incubated for 1 h with Goat anti rabbit IgG antibody conjugated to alkaline phosphatase (1:1000 dilution; Zhongshan Golden Bridge Biotechnology, China) as the second antibody. The band was visualized after reacting with Western Blue Stabilized Substrate for Alkaline Phosphatase (Promega, Madison, WI, USA) for a moment and was photographed by Tanon GIS-2020 gel image processing system (Shanghai Tanon Technology, China; Qu et al, 2016 ). The results were expressed as a relative optical density and analyzed using ImageJ software.…”