Browsing by Author "Pronrumpa Ngamsiri"

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    Arsenic impairs insulin signaling in differentiated neuroblastoma SH-SY5Y cells
    (2018-05-01) Apichaya Niyomchan; Daranee Visitnonthachai; Sumitra Suntararuks; Pronrumpa Ngamsiri; Piyajit Watcharasit; Jutamaad Satayavivad; Chulabhorn Research Institute; Faculty of Medicine, Siriraj Hospital, Mahidol University; Office of the Higher Education Commission; Chulabhorn Graduate Institute
    © 2018 A strong correlation between chronic arsenic exposure and neuropsychological disorders leads to a growing concern about a potential risk of arsenic related neurodegeneration. Evidently, brain insulin signaling contributes to physiological effects, including energy homeostasis, and learning and memory. Arsenic has been shown to impair insulin signaling in adipocytes and myocytes, however, this impairment has not yet been explored in neurons. Here we showed that NaAsO 2 caused significant reduction in basal levels of glucose, plasma membrane glucose transporter, GLUT 3 and Akt phosphorylation in differentiated human neuroblastoma SH-SY5Y cells. NaAsO 2 significantly decreased insulin-mediated glucose uptake, as well as GLUT1 and 3 membrane translocation. Furthermore, the ability of insulin to increase Akt phosphorylation, a well-recognized insulin signaling response, was significantly lessened by NaAsO 2 treatment. In addition, the classical tyrosine phosphorylation response of insulin was reduced by NaAsO 2 , as evidenced by reduction of insulin-induced tyrosine phosphorylation of insulin receptor (IR) and insulin receptor substrate-1(IRS-1). Moreover, NaAsO 2 lowered the ratio of p110, a catalytic subunit to p85, a regulatory subunit of PI3K causing an imbalance between p110 and p85, the conditions reported to contribute to insulin sensitivity. Additionally, increment of IRS-1 interaction with GSK3β, and p85-PI3K were observed in NaAsO 2 treated cells. These molecular modulations may be mechanistically attributed to neuronal insulin signaling impairment by arsenic.