Bioenergetic consequences of poly(ADP-ribose) polymerase-1 activation

Since poly (ADP-ribose) polymerase-1 (PARP-1) activation leads to depletion of ATP, we hypothesized that active glutamate uptake in astrocytes is compromised in conditions of elevated PARP-1 activity. To test this, we measured levels of ATP and glutamate uptake capacity in cultured mouse astrocytes following PARP-1 activation by the DNA alkylating agent, 1-methyl-3-nitro-1-nitroguanosine (MNNG; 100 mu M) for 30 min. ATP levels decreased with time, diminishing by 38% at 3 hr and 89% at 4 hr after MNNG exposure. Glutamate uptake capacity was declined by 86% by 4 hr after MNNG exposure. Bioenergetic depletion and declines in glutamate uptake were not observed in PARP-1(-/-) astrocyte cultures.