Effect of naloxone on the induction of immediately early genes following oxygen- and glucose-deprivation in PC12 cells.
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.
Huang
Hsueh-Meei
HM
Department of Education and Research, Taichung Veterans General Hospital, Taichung, Taiwan, ROC.
Yu
Jean-Yuan
JY
Ou
Hsio-Chung
HC
Jeng
Kee Ching
KC
D000818:Animals; D020520:Brain Infarction / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D019610:Cytoprotection / Q000187:drug effects / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics; D004660:Encephalitis / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D017781:Genes, Immediate-Early / Q000187:drug effects* / Q000235:genetics; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D007770:L-Lactate Dehydrogenase / Q000187:drug effects / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000235:genetics; D048052:Mitogen-Activated Protein Kinase 3 / Q000187:drug effects / Q000378:metabolism; D009270:Naloxone / Q000494:pharmacology* / Q000627:therapeutic use; D009292:Narcotic Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D016716:PC12 Cells; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics; D051381:Rats; D011987:Receptors, Steroid / Q000235:genetics; D015427:Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology
D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D009292:Narcotic Antagonists; D018696:Neuroprotective Agents; C539820:Nr4a1 protein, rat; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D011987:Receptors, Steroid; D009270:Naloxone; D007770:L-Lactate Dehydrogenase; D048052:Mitogen-Activated Protein Kinase 3