Effects of oxidative challenge and calcium on ATP-levels in neuronal cells.
BACKGROUND
Neurocellular overload with hydrogen peroxide (H2O2) induces oxidative stress and may initiate a cascade of intracellular toxic events leading to energy failure, increased lipid peroxidation and subsequently cell death. Studies suggest that hippocampal neurons may be more vulnerable to oxidative stress than cortical cells pointing to a differential vulnerability of neuronal cells. Since disturbed ATP- and calcium (Ca2+)-metabolism may be involved in this process, we here evaluated the effects of H2O2-induced oxidative stress and the involvement of Ca2+-regulation on neuronal energy metabolism.


METHODS
Using primary cortical and hippocampal neurons as well as immortalized hippocampal HT22 cells, we determined ATP-levels and accompanying cell death after oxidative challenge with H2O2. Additionally, the combined effects of H2O2 and alterations in Ca2+-concentrations were pharmacologically characterized in more detail.


RESULTS
H2O2-incubation decreased ATP-levels in a dose- and time-dependent manner in all neuronal cell systems tested. Such effects were most pronounced in primary hippocampal neurons. In cortical cells, increased ATP-levels were notable under low H2O2-concentrations. A dose-dependent decrease in ATP-concentrations was observed after treatment with Ca2+, which was further enhanced by additional H2O2-challenge.


CONCLUSIONS
Our data underline that both, H2O2- and Ca2+-treatment, are able to disturb intracellular energy metabolism. Out of the different systems studied, the ATP-decrease is most pronounced in hippocampal primary neurons, suggesting that this mechanism contributes to the selective neuronal vulnerability to oxidative stress in these neurons.
Teepker
Michael
M
Department of Psychiatry and Psychotherapy, Philipps-University, Marburg, Germany.
Anthes
Norman
N
Fischer
Sabine
S
Krieg
Jürgen-Christian
JC
Vedder
Helmut
H
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000633:toxicity*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D016877:Oxidants / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism
D016877:Oxidants; D017382:Reactive Oxygen Species; D000255:Adenosine Triphosphate; D006861:Hydrogen Peroxide; D002118:Calcium