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Modulation of rat hippocampal neurons by H2O2‐mediated oxidative stress
Author(s) -
Gerich Florian J,
Müller Michael
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a793-a
Subject(s) - ruthenium red , oxidative stress , redox , mitochondrion , superoxide , biophysics , chemistry , membrane potential , intracellular , reactive oxygen species , hippocampal formation , thapsigargin , microbiology and biotechnology , oxidative phosphorylation , calcium , biochemistry , biology , endocrinology , enzyme , organic chemistry
Superoxide released from dysfunctioning mitochondria is converted to H 2 O 2 , 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 H 2 O 2 ‐mediated responses of hippocampal neurons. Oxidation of redox‐sensitive dyes confirmed the membrane permeability of H 2 O 2 in cultured neurons and acute slices, thus H 2 O 2 may not only act at its generation site but may affect neighboring cells as well. 1 mM H 2 O 2 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 H 2 O 2 and NADH was apparently directly oxidized. In cultured neurons 0.2 mM H 2 O 2 moderately increased the intracellular Ca 2+ concentration. This Ca 2+ rise was not prevented by 2 mM Ni 2+ , Ca 2+ ‐free solution, mitochondrial uncoupling by 1 μM FCCP or chelating Fe 2+ . Yet it was partially reduced by 1–5 μM thapsigargin and by 10 μM ruthenium red. In conclusion, low levels of H 2 O 2 release Ca 2+ from internal stores, which need to be identified by further analyses. The observed modulation of Ca 2+ 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. Supported by the DFG (SFB 406 and CMPB)