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Citation
Singh, P., Chowdhuri, D.K. (2018). Modulation of sestrin confers protection to Cr(VI) induced neuronal cell death in Drosophila melanogaster.  Chemosphere 191(): 302--314.
FlyBase ID
FBrf0237331
Publication Type
Research paper
Abstract

Increased oxidative stress is one of the major causes of hexavalent chromium Cr(VI), a heavy metal with diverse applications and environmental presence, induced neuronal adversities in exposed organism including Drosophila. Sestrin (sesn), an oxidative stress responsive gene, emerges as a novel player in the management of oxidative stress response. It is reported to be regulated by Target of rapamycin (TOR) and the former regulates autophagy and plays an important role in the prevention of neurodegeneration. Due to limited information regarding the role of sesn in chemical induced cellular adversities, it was hypothesized that modulation of sesn may improve the Cr(VI) induced neuronal adversities in Drosophila. Upon exposure of Cr(VI) (5.0-20.0 μg/ml) to D. melanogaster larvae (w1118; background control), neuronal cell death was observed at 20.0 μg/ml of Cr(VI) concentration which was found to be reversed by targeted sesn overexpression (Elav-GAL4>UAS-sesn) in those cells of exposed organism by the induction of autophagy concomitant with decreased reactive oxygen species (ROS) level, p-Foxo-, p-JNK- and p-Akt-levels with decreased apoptosis. Conversely, after sesn knockdown (Elav-GAL4>UAS-sesnRNAi) in neuronal cells, they become more vulnerable to oxidative stress and apoptosis. Furthermore, knockdown of sesn in neuronal cells of exposed organism resulted in decreased autophagy with increased TOR and p-S6k levels while overexpression of sesn led to their decreased levels suggestive of decreased anabolic and increased catabolic activity in neuronal cells shifting energy towards the augmentation of cellular repair. Taken together, the study suggests therapeutic implications of sesn against chemical induced neuronal adversities in an organism.

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    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Chemosphere
    Title
    Chemosphere
    Publication Year
    1972-
    ISBN/ISSN
    0045-6535
    Data From Reference
    Genes (13)