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 |
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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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