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iption Factor NF-κB Caused by Acute Hypoxia in the Heart

Journal of the Korean Pediatric Society 2002;45(9):1106-1113.
Published online September 15, 2002.
iption Factor NF-κB Caused by Acute Hypoxia in the Heart
Chan Uhng Joo, Woo Suk Juhng, Jae Cheol Kim, Ho Keun Yi
Department of Pediatrics, Institute of Cardiovascular Research, Medical School, Chonbuk National University, Jeonju, Korea
급성 저산소증 상태에서 심장 내전사인자 NF-κB의 기능
주찬웅, 정우식, 김재철, 이호근
전북대학교 의과대학 소아과학교실, 심혈관연구소
Correspondence: 
Chan Uhng Joo, Email: joocu@moak.chonbuk.ac.kr
Abstract
Purpose
: Nuclear factor-κB(NF-κB) 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-κB 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-κB, 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-κB in the heart, the rats also were pretreated with diethyl-dithiocarbamic acid(DDTC) into peritoneal cavity to block NF-κB translocation into nucleus.
Results
: The expression of NF-κB, 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-κB translocation reduced those expressions of VEGF and IGF-I.
Conclusion
: These results suggest that NF-κB has a protective role against the acute hypoxia through several gene expression, especially VEGF and IGF-I in heart muscle.
Key Words: NF-Κb, Hypoxia, VEGF, IGF-I


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