Gene expression in mouse brain following chronic hypoxia: role of sarcospan in glial cell death.
Hypoxia is a hallmark of respiratory, neurological, or hematological diseases as well as life at high altitude. For example, chronic constant hypoxia (CCH) occurs in chronic lung diseases or at high altitude, whereas chronic intermittent hypoxia (CIH) occurs in diseases such as sleep apnea or sickle cell disease. Despite the fact that such conditions are frequent, the cellular and molecular mechanisms underlying the effect of hypoxia, whether constant or intermittent, are not well understood. In this study, we first determined the effect of CCH and CIH on global gene expression in different regions of mouse brain using microarrays and then investigated the biological role of genes of interest. We found that: 1) in the cortical region, the expression level of 80 genes was significantly altered by CIH (16 up- and 64 downregulated), and this number increased to 137 genes following CCH (34 up- and 103 downregulated); 2) a similar number of gene alterations was identified in the hippocampal area, and the majority of the changes in this region were upregulations; 3) two genes (Sspn and Ttc27) were downregulated in both brain regions and following both treatments; and 4) RNA interference-mediated knockdown of Sspn increased cell death in hypoxia in a cell culture system. We conclude that CIH or CCH induced significant and distinguishable alterations in gene expression in cortex and hippocampus and that Sspn seems to play a critical role in inducing cell death under hypoxic conditions.
Department of Pediatrics (Section of Respiratory Medicine) and Neuroscience, University of California San Diego, La Jolla, CA 92093-0735, USA.
Dan
D
Zhou
Jiyi
J
Wang
Matthew A
MA
Zapala
Jin
J
Xue
Nicholas J
NJ
Schork
Gabriel G
GG
Haddad
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D001253:Astrocytes / Q000473:pathology*; D001273:Atmosphere Exposure Chambers; D001921:Brain / Q000254:growth & development; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D015687:Cell Hypoxia / Q000235:genetics / Q000502:physiology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002908:Chronic Disease; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D005910:Glioma / Q000473:pathology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000860:Hypoxia / Q000235:genetics* / Q000473:pathology; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D051379:Mice; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D010100:Oxygen / Q000008:administration & dosage / Q000494:pharmacology; D034622:RNA Interference; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D002352:Carrier Proteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; C491632:Sspn protein, mouse; D010100:Oxygen