The Federation of American Societies for Experimental Biology
FASEB Journal vol:20 issue:4 pages:A793-A793
85th Annual Meeting of the DPG location:Munich date:26-29 March 2006
Superoxide released from dysfunctioning mitochondria is converted to H2O2, which modulates cellular redox status and redox-sensitive proteins. Such redox signaling occurs under pathophysiological conditions, but is also part of normal signaling. Here we analyzed the H2O2-mediated responses of hippocampal neurons. Oxidation of redox-sensitive dyes confirmed the membrane permeability of H2O2 in cultured neurons and acute slices, thus H2O2 may not only act at its generation site but may affect neighboring cells as well. 1 mM H2O2 postponed the onset of hypoxic spreading depression, but did not depress basal synaptic function or paired-pulse facilitation. Mitochondria depolarized only slightly in response to 1 mM H2O2 and NADH was apparently directly oxidized. In cultured neurons 0.2 mM H2O2 moderately increased the intracellular Ca2+ concentration. This Ca2+ rise was not prevented by 2 mM Ni2+, Ca2+-free solution, mitochondrial uncoupling by 1 µM FCCP or chelating Fe2+. Yet it was partially reduced by 1–5 µM thapsigargin and by 10 µM ruthenium red. In conclusion, low levels of H2O2 release Ca2+ from internal stores, which need to be identified by further analyses. The observed modulation of Ca2+ sequestration by redox status and ROS levels could play a pivotal role in adjusting cellular function to oxidative stress and it may contribute to the sensing of metabolic disturbances.