Expression of hypoxia-inducible factor-1 in the cochlea of newborn rats.
Hypoxia/ischemia is a major pathogenetic factor in the development of hearing loss. An important transcription factor involved in the signaling and adaptation to hypoxia/ischemia is the hypoxia-inducible factor-1 (HIF-1). To study HIF-1 expression we used an in vitro hypoxia model of explant and dissociated cultures of the stria vascularis, the organ of Corti with limbus and the modiolus from the cochlea of 3-5-day-old Wistar rats. Hypoxia differentially increased HIF-1 activity as measured by a reporter gene. Twenty-four hour hypoxia increased HIF-1 activity 14.1+/-3.5-fold in the modiolus, 9.4+/-3.0-fold in the organ of Corti with limbus, and 6.4+/-1.5-fold in the stria vascularis. The HIF-1alpha mRNA level was measured by quantitative reverse transcription polymerase chain reaction and showed a lower expression in the modiolus (1.3+/-0.2 pg/microg RNA) than in both the organ of Corti with limbus and the stria vascularis (2.7-3.2+/-1.3, P<0.01). Hypoxia had no effect on the HIF-1alpha mRNA levels. The region-specific regulation of HIF-1 expression on the transcriptional and posttranslational levels may expand the possibilities for adaptation of the cochlea to hypoxia.
D000818:Animals; D002478:Cells, Cultured; D003051:Cochlea / Q000166:cytology / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression; D017930:Genes, Reporter; D034381:Hearing Loss / Q000209:etiology / Q000378:metabolism*; D006651:Histocytochemistry; D000860:Hypoxia / Q000150:complications / Q000378:metabolism*; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007150:Immunohistochemistry; D008156:Luciferases / Q000378:metabolism; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics; D009924:Organ Culture Techniques; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D014162:Transfection
D004268:DNA-Binding Proteins; C497444:Hif1a protein, rat; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D008156:Luciferases