Distinct role of Hsp70 in Drosophila hemocytes during severe hypoxia

Abstract

Severe hypoxia can lead to injury and mortality in vertebrate or invertebrate organisms. Our research is focused on understanding the molecular mechanisms that lead to injury or adaptation to hypoxic stress using Drosophila as a model system. In this study, we employed the UAS-Gal4 system to dissect the protective role of Hsp70 in specific tissues in vivo under severe hypoxia. In contrast to overexpression in tissues such as muscles, heart, and brain, we found that overexpression of Hsp70 in hemocytes of flies provides a remarkable survival benefit to flies exposed to severe hypoxia for days. Furthermore, these flies were tolerant not only to severe hypoxia but also to other stresses such as oxidant stress (e.g., paraquat feeding or hyperoxia). Interestingly we observed that the better survival with Hsp70 overexpression in hemocytes under hypoxia or oxidant stress is causally linked to reactive oxygen species (ROS) reduction in whole flies. We also show that hemocytes are a major source of ROS generation, leading to injury during hypoxia, and their elimination results in a better survival under hypoxia. Hence, our study identified a protective role for Hsp70 in Drosophila hemocytes, which is linked to ROS reduction in the whole flies and thus helps in their remarkable survival during oxidant or hypoxic stress.