title: Neuroglobin-overexpression alters hypoxic response gene expression in primary neuron culture following oxygen glucose deprivation.
abstract: Neuroglobin (Ngb) is a tissue globin specifically expressed in neurons. Our laboratory and others have shown that Ngb overexpression protects neurons against hypoxia/ischemia, but the underlying mechanisms remain poorly understood. Recent studies demonstrate that hypoxia/ischemia induces a multitude of spatially and temporally regulated responses in gene expression, and initial evidence suggested that Ngb might function in altering biological processes of gene expression. In this study, we asked how Ngb may help regulate genes responsive to hypoxia. Expression of hypoxic response genes following oxygen-glucose deprivation (OGD) was examined using mRNA arrays in neuroglobin-overexpressing transgenic (Ngb-Tg) and wild type (WT) mouse neurons. From a total of 113 genes on the microarray, mRNA expression of 65 genes was detected. Under rest condition, 14 genes were downregulated in Ngb-Tg neurons compared to WT. In WT neurons, after 4-h OGD followed by 4-h reoxygenation (O4/R4), 20 genes were significantly downregulated, and only Fos mRNA was significantly increased. However, out of the 20 downregulated genes in WT neurons, 12 of them were no longer significantly changed in Ngb-Tg neurons: Add1, Arnt2, Camk2g, Cstb, Dr1, Epas1, Gna11, Hif1a, Il6st, Khsrp, Mars and Rara. Among these 12 genes, 8 (Add1, Camk2g, Cstb, Dr1, Epas1, Gna11, Hif1a, Khsrp) were already reduced in Ngb-Tg neurons compared to WT under rest conditions. Additionally, three genes that initially showed no changes in WT neurons (Ctgf, Egfr and Pea15) were downregulated after OGD in the Ngb-Tg neurons. These findings suggest that Ngb overexpression modulates mRNA expression of multiple hypoxic response genes in the early phase after OGD/reoxygenation. Further studies on these gene networks and interactions may lead to better understanding of Ngb in signaling pathways that contribute to neuroprotection.
authors.affiliation: Neuroprotection Research Laboratory, Department of Neurology and Radiology, Massachusetts General Hospital, Program in Neuroscience, Harvard Medical School, 149 13th Street, Room 2411A, Charlestown, MA 02129, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Yu
authors.forename: J
authors.initials: J
authors.lastname: Liu
authors.forename: S
authors.initials: S
authors.lastname: Guo
authors.forename: C
authors.initials: C
authors.lastname: Xing
authors.forename: X
authors.initials: X
authors.lastname: Fan
authors.forename: M
authors.initials: M
authors.lastname: Ning
authors.forename: J C
authors.initials: JC
authors.lastname: Yuan
authors.forename: E H
authors.initials: EH
authors.lastname: Lo
authors.forename: X
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D015687:Cell Hypoxia; D002470:Cell Survival / Q000235:genetics; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D003470:Culture Media; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D005914:Globins / Q000096:biosynthesis* / Q000235:genetics; D005947:Glucose / Q000172:deficiency; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D000078787:Neuroglobin; D009474:Neurons / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress / Q000235:genetics; D010100:Oxygen / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D014158:Transcription, Genetic
chemical_list: D003470:Culture Media; D009419:Nerve Tissue Proteins; D000078787:Neuroglobin; D012333:RNA, Messenger; D005914:Globins; D005947:Glucose; D010100:Oxygen