Hypoxia and nitric oxide induce a rapid, reversible cell cycle arrest of the drosophila syncytial divisions

Cells can respond to reductions in oxygen (hypoxia) by metabolic adaptation s, quiescence or cell death (1), The nuclear division cycles of syncytial s tage Drosophila melanogaster embryos reversibly arrest upon hypoxia, We exa mined this rapid arrest in real time using a fusion of green fluorescent pr otein and histone 2A In addition to an interphase arrest, mitosis was speci fically blocked in metaphase, much like a checkpoint arrest. Nitric oxide, recently proposed as a hypoxia signal in Drosophila, induced a reversible a rrest of the nuclear divisions comparable with that induced by hypoxia. Syn cytial stage embryos die during prolonged hypoxia, whereas post-gastrulatio n embryos (cellularized) survive (2, 3). We examined ATP levels and morphol ogy of syncytial and cellularized embryos arrested by hypoxia, nitric oxide , or cyanide. Upon oxygen deprivation, the ATP levels declined only slightl y in cellularized embryos and more substantially in syncytial embryos. Reve rsal of hypoxia restored ATP levels and relieved the cell cycle and develop mental arrests. However, morphological abnormalities suggested that syncyti al embryos suffered irreversible disruption of developmental programs. Our results suggest that nitric oxide plays a role in the response of the syncy tial embryo to hypoxia but that it is not the sole mediator of these respon ses.