Olanzapine protects PC12 cells from oxidative stress induced by hydrogen peroxide.
Neuroanatomical studies suggest that neuronal atrophy and destruction occur over the course of many years in neurodegenerative conditions such as schizophrenia and Alzheimer's disease. In schizophrenia, early intervention with atypical neuroleptics such as olanzapine has been shown to prevent development of some of the more serious and debilitating symptoms in many patients. The mechanisms whereby olanzapine slows or prevents symptom progression in schizophrenia remain unclear. A previous study found that olanzapine increased mRNA for the copper/zinc isoform of the superoxide dismutase enzyme (SOD-1). We investigated the effects of olanzapine in PC12 cells exposed to hydrogen peroxide. We measured cell viability, observed evidence of necrosis and apoptosis, checked the SOD-1 mRNA by Northern blot analyses, and determined SOD-1 enzyme activity. We found that: (1) the decrease in cell viability induced by hydrogen peroxide was attenuated in PC12 cells pretreated with olanzapine; (2) olanzapine increased SOD enzyme activity in PC12 cells; (3) inhibiting SOD activity with diethyldithiocarbamic acid prevented the cytoprotective actions of olanzapine; and (4) the decrease in SOD-1 mRNA level induced by hydrogen peroxide was blocked by pretreatment with olanzapine. These data indicate that the neuroprotective action of olanzapine includes the upregulation of SOD.
Wei
Zelan
Z
Neuropsychiatric Research Unit, Department of Psychiatry, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
Bai
Ou
O
Richardson
J Steven
JS
Mousseau
Darrell D
DD
Li
Xin-Min
XM
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001569:Benzodiazepines; D002470:Cell Survival / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology; D000077152:Olanzapine; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D016716:PC12 Cells; D010890:Pirenzepine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D000072105:Superoxide Dismutase-1
D014150:Antipsychotic Agents; D018696:Neuroprotective Agents; D016877:Oxidants; D012333:RNA, Messenger; D001569:Benzodiazepines; D010890:Pirenzepine; D006861:Hydrogen Peroxide; C000606292:Sod1 protein, rat; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D000077152:Olanzapine