PMID- 16479386 OWN - NLM STAT- MEDLINE DCOM- 20070130 LR - 20181113 IS - 0017-6192 (Print) IS - 0017-6192 (Linking) VI - 54 IP - 9 DP - 2006 Sep TI - [Influence of ischemia/hypoxia on the HIF-1 activity and expression of hypoxia-dependent genes in the cochlea of the newborn rat]. PG - 689-97 AB - BACKGROUND: Transcription factor HIF-1 (hypoxia-inducible factor-1) regulates the expression of genes which are involved in glucose supply, growth, metabolism, redox reactions and blood supply. Hypoxia and ischemia play an important role in the pathogenesis of tinnitus and hearing loss. Therefore, HIF-1 activity and the expression of HIF-1 dependent genes in the cochlea were examined under ischemic and hypoxic conditions. MATERIAL AND METHODS: For the HIF-1 analysis, single-cell cultures of the organ of Corti (OC), stria vascularis (SV) and modiolus (MOD) were used. mRNA expression was analyzed in the organotypic culture using a microarray technique (RN U34-chip, Affymetrix). RESULTS: Ischemia (hypoxia without glucose) and pure hypoxia increase the HIF-1 activity identically, with the highest increase found in MOD and OC. The HIF-1 alpha mRNA levels were found to be higher in SV than in the OC and MOD. During culturing, there is a clear increase in HIF-1 alpha mRNA and the expression of a number of HIF-1 dependent genes, such as Gapdh/glyceraldehyde-3-phosphate dehydrogenase, Slc2a1/solute carrier family 2 (facilitated glucose transporter), member 1, Tf/transferrin and Tfrc/transferrin receptor, in all three regions. In SV, MOD and OC, increase in the expression of Hmox1/hemoxygenase 1, Nos2/nitric oxide synthase, inducible and Tfrc is particularly high. Hypoxia (5 h) results in an increased expression of Igf2/Insulin-like growth factor 2. CONCLUSION: The present data underline the contribution of radical forming processes to the pathogenesis of inner ear diseases. For experimental research, it is important to note that organotypic culture may be coupled with hypoxia. FAU - Mazurek, B AU - Mazurek B AD - Molekularbiologisches Forschungslabor der HNO-Klinik, Charite--Universitatsmedizin Berlin. FAU - Rheinlander, C AU - Rheinlander C FAU - Fuchs, F-U AU - Fuchs FU FAU - Amarjargal, N AU - Amarjargal N FAU - Kuban, R-J AU - Kuban RJ FAU - Ungethum, U AU - Ungethum U FAU - Haupt, H AU - Haupt H FAU - Kietzmann, T AU - Kietzmann T FAU - Gross, J AU - Gross J LA - ger PT - Journal Article TT - Einfluss von Ischamie/Hypoxie auf die HIF-1-Aktivitat und Expression von hypoxieabhangigen Genen in der Kochlea der neugeborenen Ratte. PL - Germany TA - HNO JT - HNO JID - 2985099R RN - 0 (Hypoxia-Inducible Factor 1) SB - IM MH - Animals MH - Animals, Newborn MH - Cell Hypoxia MH - Cells, Cultured MH - Cochlea/*metabolism MH - Gene Expression Regulation MH - Hypoxia/*metabolism MH - Hypoxia-Inducible Factor 1/*metabolism MH - Ischemia/*metabolism MH - Rats MH - Rats, Wistar EDAT- 2006/02/16 09:00 MHDA- 2007/01/31 09:00 CRDT- 2006/02/16 09:00 PHST- 2006/02/16 09:00 [pubmed] PHST- 2007/01/31 09:00 [medline] PHST- 2006/02/16 09:00 [entrez] AID - 10.1007/s00106-005-1371-6 [doi] PST - ppublish SO - HNO. 2006 Sep;54(9):689-97. doi: 10.1007/s00106-005-1371-6.