Abstract
Overproduction of the deleterious reactive oxygen species (ROS) is one of the major causes of mercury, a heavy metal with diverse applications and environmental presence, induced neuronal and gastrointestinal adversities in exposed organism including Drosophila melanogaster. Sestrin, an oxidative stress responsive gene, emerges as a novel player in the management of oxidative stress response. Due to limited information regarding the role of sestrin in mercury-induced gastrointestinal adversities, it was hypothesized that modulation of sestrin may improve the mercury-induced gastrointestinal adversities in Drosophila. Here, we fed Drosophila with 400 μM HgCl2 and found that sestrin transcriptional level was significantly increased in midguts. Sestrin knockdown in HgCl2-exposed midguts decreased survival rates and climbing ability of flies, and inhibited superoxide dismutase and glutathione-S-transferase activities of midgut epithelieum. Meanwhile, sestrin knockdown in midgut aggravated the HgCl2-induced disruption of intestinal organization by worsening ROS production and cell apoptosis. Immunohistochemical staining data revealed that sestrin knockdown inhibited intestinal stem cell division in HgCl2-exposed midguts. Furthermore, JNK signaling was found to mediated sestrin expression in midgut. Taken together, the study demonstrated that sestrin protects Drosophila midgut from HgCl2-induced oxidative damage by inhibiting ROS production and stimulating the tissue regeneration program under regulation of JNK signaling pathway. This work suggests therapeutic implications of sestrin against heavy metal-induced gastrointestinal adversities in mammals.
