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/mug 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-1 alpha 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. (C) 2003 Elsevier B.V. All rights reserved.