Role of the Nuclear Transcription Factor NF-kappa B Caused by Acute Hypoxia in the Heart

ABSTRACT

PURPOSE: Nuclear factor-kappa B(NF-kappa B) is now recognized as playing a potential role in programmed cell death and the adaptive response to various stress. Cellular hypoxia is a primary manifestation of many cardiovascular diseases. It seems that vascular endothelial growth factor (VEGF) and insulin like growth factor-I(IGF-I) have a function as a protective molecule in the heart against several stress including hypoxia. In this study, the role of NF-kappa B to the cellular response and regulation of protective molecules against the acute hypoxia in the heart was studied. METHODS: To cause acute hypoxic stress to the heart, Sprague Dawley rats were exposed to hypoxic chamer(N2 92% and O2 8%). After the hypoxic exposure, nuclear proteins, total proteins and mRNA were isolated from heart. Translocation of the transcription factors NF-kappa B, NF-ATc, AP-1 and NKX-2.5 were evaluated by electrophoretic mobility shift assay(EMSA). The expression of IGF-I and VEGF were studied before and after the hypoxic stress by competitive-PCR, Northern hybridization and Western hybridization. To confirm the role of the NF-kappa B in the heart, the rats also were pretreated with diethyl-dithiocarbamic acid(DDTC) into peritoneal cavity to block NF-kappa B translocation into nucleus. RESULTS: The expression of NF-kappa B, AP-1 and NF-ATc were increased by the hypoxic stress. Increased expression of the VEGF and IGF-I were also observed by the hypoxic stress. However, the blocking of the NF-kappa B translocation reduced those expressions of VEGF and IGF-I. CONCLUSION: These results suggest that NF-kappa B has a protective role against the acute hypoxia through several gene expression, especially VEGF and IGF-I in heart muscle.