Delta opioid agonist [D-Ala2, D-Leu5] enkephalin (DADLE) reduced oxygen-glucose deprivation caused neuronal injury through the MAPK pathway.
It has been demonstrated that [D-Ala2, D-Leu5] enkephalin (DADLE), a delta opioid agonist, protected neuron from hypoxic neuronal injury by activating the delta opioid receptor (DOR). However, whether DADLE can prevent neuronal injury induced by severe hypoxia like oxygen-glucose deprivation (OGD) is not clear. Here, we investigated whether DADLE has a protective effect against neuronal injury induced by oxygen-glucose deprivation. Neuron viability was measured by MTT and neuron injury was assessed by lactate dehydrogenase (LDH) release. Protein expression was examined by Western blot. The results showed that DADLE protected the cortical neuron in a dose-dependent way from OGD injury. And this neuroprotective effect could be completely blocked by delta 2 opioid antagonist Naltrindole. DADLE increased phosphorylation of ERK and prevented OGD-induced p38 phosphorylation. Neither DADLE nor Naltrindole had any appreciable effect on phosphorylation of JNK. One of the protective mechanisms of DADLE on OGD neurons may be due to the dynamic balance between the activation of ERK and the p38.
Ke
Sun
S
Department of Anesthesiology, RenJi Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Dian-san
Su
S
Xiang-rui
Wang
W
D000818:Animals; D001930:Brain Injuries; D015687:Cell Hypoxia / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D016308:Enkephalin, Leucine-2-Alanine / Q000008:administration & dosage / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005947:Glucose / Q000172:deficiency*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017465:Receptors, Opioid, delta / Q000819:agonists* / Q000037:antagonists & inhibitors; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D009292:Narcotic Antagonists; D018696:Neuroprotective Agents; D017465:Receptors, Opioid, delta; D009271:Naltrexone; D016308:Enkephalin, Leucine-2-Alanine; D007770:L-Lactate Dehydrogenase; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C055382:naltrindole; D005947:Glucose