R. Malhotra et al., Hypoxia induces apoptosis via two independent pathways in Jurkat cells: differential regulation by glucose, AM J P-CELL, 281(5), 2001, pp. C1596-C1603
Glucose uptake and metabolism inhibit hypoxia-induced apoptosis in a variet
y of cell types, but the underlying molecular mechanisms remain poorly unde
rstood. In the present study, we explore hypoxia-mediated cell death pathwa
ys in Jurkat cells in the presence and absence of extracellular glucose. In
the absence of extracellular glucose, hypoxia caused cytochrome c release,
caspase 3 and poly(ADP-ribose) polymerase cleavage, and DNA fragmentation;
this apoptotic response was blocked by the caspase 9 inhibitor z-LEHD-FMK.
The presence of extracellular glucose during hypoxia prevented cytochrome
c release and activation of caspase 9 but did not prevent apoptosis in Jurk
at cells. In these conditions, overexpression of the caspase 8 inhibitor v-
FLIP prevented hypoxia-mediated cell death. Thus hypoxia can stimulate two
apoptotic pathways in Jurkat cells, one dependent on cytochrome c release f
rom mitochondria that is prevented by glucose uptake and metabolism, and th
e other independent of cytochrome c release and resulting from activation o
f the death receptor pathway, which is accelerated by glucose uptake and me
tabolism.