Anisomycin protects cortical neurons from prolonged hypoxia with differential regulation of p38 and ERK.
MAP kinase is associated with delta-opioid receptor (DOR) signaling and plays a role in cell survival/death. Since anisomycin may alter MAP kinase activity and affect neuronal survival, we investigated whether anisomycin alters neuronal response to hypoxic stress and DOR inhibition. The experiments were performed in cultured cortical neurons. MAP kinase activities were determined by immunoblotting and neuronal viability was assessed by LDH leakage and live/dead morphological study. DOR inhibition with naltrindole (10 microM) led to significant injury in normoxic neurons after 24 h of treatment and exacerbated hypoxia-induced injury. Along with the injury, either by hypoxia or naltrindole, phosphorylated p38 increased in a major way, while phosphorylated ERK and JNK had no significant change or slightly decreased. Anisomycin (50 ng/ml) prevented the increase in phosphorylated p38 immunoreactivity induced by naltrindole and reduced the neuronal injury. The results suggest that (1) MAP kinases are differentially involved in neuronal response to hypoxia and DOR inhibition in cortical neurons with phosphorylated p38 immunoreactivity being upregulated and (2) anisomycin attenuates the increase in phosphorylated p38 immunoreactivity and reduces neuronal injury induced by hypoxia and DOR inhibition.
Hong
Soon-Sun
SS
Department of Pediatrics, Yale University School of Medicine, New Haven, CT 06520, USA.
Qian
Hong
H
Zhao
Peng
P
Bazzy-Asaad
Alia
A
Xia
Ying
Y
D000818:Animals; D000841:Anisomycin / Q000494:pharmacology*; D015687:Cell Hypoxia / Q000187:drug effects*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000473:pathology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000187:drug effects*; D005333:Fetus; D015151:Immunoblotting; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D048051:p38 Mitogen-Activated Protein Kinases / Q000187:drug effects*
D009292:Narcotic Antagonists; D018696:Neuroprotective Agents; D009271:Naltrexone; D000841:Anisomycin; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C055382:naltrindole