The anoxia-tolerant fruit fly, Drosophila melanogaster, has routinely been used to examine cellular mechanisms responsible for anoxic and oxidative stress resistance. Nitric oxide (NO), an important cellular signaling molecule, and its downstream activation of cGMP-dependent protein kinase G (PKG) has been implicated as a protective mechanism against ischemic injury in diverse animal models from insects to mammals. In Drosophila, increased PKG signaling results in increased survival of animals exposed to anoxic stress. To determine if activation of the NO/cGMP/PKG pathway is protective at the cellular level, the present study employed a pharmacological protocol to mimic hypoxic injury in Drosophila S2 cells. The commonly used S2 cell line was derived from a primary culture of late stage (20-24 h old) Drosophila melanogaster embryos. Hypoxic stress was induced by exposure to either sodium azide (NaN3) or cobalt chloride (CoCl2). During chemical hypoxic stress, NO/cGMP/PKG activation protected against cell death and this mechanism involved modulation of downstream mitochondrial ATP-sensitive potassium ion channels (mitoKATP). The cellular protection afforded by NO/cGMP/PKG activation during ischemia-like stress may be an adaptive cytoprotective mechanism and modulation of this signaling cascade could serve as a potential therapeutic target for protection against hypoxia or ischemia-induced cellular injury.
Keywords: Cobalt chloride; Fruit fly; Hypoxia; Mitochondria; cGMP-dependent protein kinase; mitoK(ATP) ion channels.
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