Pj. Digregorio et al., Hypoxia and nitric oxide induce a rapid, reversible cell cycle arrest of the drosophila syncytial divisions, J BIOL CHEM, 276(3), 2001, pp. 1930-1937
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.