PMID- 18457920 OWN - NLM STAT- MEDLINE DCOM- 20080919 LR - 20131121 IS - 0304-3940 (Print) IS - 0304-3940 (Linking) VI - 438 IP - 2 DP - 2008 Jun 20 TI - Effect of naloxone on the induction of immediately early genes following oxygen- and glucose-deprivation in PC12 cells. PG - 252-6 LID - 10.1016/j.neulet.2008.04.036 [doi] AB - Cerebral ischemia/reperfusion involves inflammatory process and naloxone is able to reduce infarct volume and has been used as a therapeutic agent for brain injury. Hypoxia induces the immediate early genes (IEGs) rapidly and transiently that may initiate a cascade of cellular responses that are necessary for survival and normal function. However, the protective effect of naloxone on ischemic/hypoxic neuronal cells was only partly studied. Thus, the effects of naloxone on oxygen- and glucose-deprivation (OGD) and OGD followed by reoxygenation (OGD/R) on the expression of IEGs were examined in PC12 cells. The result showed that lactate dehydrogenase (LDH) released in the media was reduced by naloxone. The temporal response of IEG mRNA encoding c-fos, c-jun, nur77, and zif268 was induced with different degree of intensity following hypoxia, whereas the level of GAPDH mRNA was relatively constant. However, these signals of c-fos, c-jun, and nur77 by hypoxia were reduced significantly by naloxone. Treatment with OGD also activated mitogen-activated protein kinase (MAPK) pathway. The induction of c-fos, c-jun, nur77, and zif268 by hypoxia was inhibited by naloxone (0.1 microM) and MAPK inhibitors (10 microM of U0126, D98059, SB203580). However, naloxone increased the expression of ERK1/2 by OGD concomitantly diminished the LDH release. Thus, the present studies demonstrated that OGD induced IEGs including c-fos, c-jun, nur77, and zif268 and MAPK signaling pathways were regulated differently by naloxone. FAU - Huang, Hsueh-Meei AU - Huang HM AD - Department of Education and Research, Taichung Veterans General Hospital, Taichung, Taiwan, ROC. FAU - Yu, Jean-Yuan AU - Yu JY FAU - Ou, Hsio-Chung AU - Ou HC FAU - Jeng, Kee Ching AU - Jeng KC LA - eng PT - Journal Article DEP - 20080416 PL - Ireland TA - Neurosci Lett JT - Neuroscience letters JID - 7600130 RN - 0 (DNA-Binding Proteins) RN - 0 (Enzyme Inhibitors) RN - 0 (Narcotic Antagonists) RN - 0 (Neuroprotective Agents) RN - 0 (Nr4a1 protein, rat) RN - 0 (Nuclear Receptor Subfamily 4, Group A, Member 1) RN - 0 (Proto-Oncogene Proteins c-fos) RN - 0 (Proto-Oncogene Proteins c-jun) RN - 0 (Receptors, Steroid) RN - 36B82AMQ7N (Naloxone) RN - EC 1.1.1.27 (L-Lactate Dehydrogenase) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3) SB - IM MH - Animals MH - Brain Infarction/drug therapy/metabolism/physiopathology MH - Cytoprotection/drug effects/physiology MH - DNA-Binding Proteins/genetics MH - Encephalitis/drug therapy/metabolism/physiopathology MH - Enzyme Inhibitors/pharmacology MH - Gene Expression Regulation/*drug effects MH - Genes, Immediate-Early/*drug effects/genetics MH - Hypoxia-Ischemia, Brain/*drug therapy/*metabolism/physiopathology MH - L-Lactate Dehydrogenase/drug effects/metabolism MH - MAP Kinase Signaling System/drug effects/genetics MH - Mitogen-Activated Protein Kinase 3/drug effects/metabolism MH - Naloxone/*pharmacology/therapeutic use MH - Narcotic Antagonists/pharmacology/therapeutic use MH - Neurons/*drug effects/metabolism MH - Neuroprotective Agents/pharmacology/therapeutic use MH - Nuclear Receptor Subfamily 4, Group A, Member 1 MH - Oxidative Stress/drug effects/physiology MH - PC12 Cells MH - Proto-Oncogene Proteins c-fos/genetics MH - Proto-Oncogene Proteins c-jun/genetics MH - Rats MH - Receptors, Steroid/genetics MH - Reperfusion Injury/drug therapy/metabolism/physiopathology EDAT- 2008/05/07 09:00 MHDA- 2008/09/20 09:00 CRDT- 2008/05/07 09:00 PHST- 2007/10/26 00:00 [received] PHST- 2008/03/28 00:00 [revised] PHST- 2008/04/11 00:00 [accepted] PHST- 2008/05/07 09:00 [pubmed] PHST- 2008/09/20 09:00 [medline] PHST- 2008/05/07 09:00 [entrez] AID - S0304-3940(08)00508-9 [pii] AID - 10.1016/j.neulet.2008.04.036 [doi] PST - ppublish SO - Neurosci Lett. 2008 Jun 20;438(2):252-6. doi: 10.1016/j.neulet.2008.04.036. Epub 2008 Apr 16.