4-O-methylascochlorin, methylated derivative of ascochlorin, stabilizes HIF-1 alpha via AMPK activation
- Authors
- Jeong, JH[Jeong, Ji-Hak]; Kang, JH[Kang, Jeong Han]; Hwang, SL[Hwang, Seung-Lark]; Cho, HJ[Cho, Hyun-Ji]; Park, KK[Park, Kwan-Kyu]; Park, YY[Park, Yoon-Yup]; Chung, IK[Chung, Il-Kyung]; Chang, HW[Chang, Hyeun-Wook]; Kim, CH[Kim, Cheorl-Ho]; Min, KS[Min, Kwan-Sik]; Kim, HD[Kim, Hong-Duck]; Magae, J[Magae, Junji]; Kang, SS[Kang, Shin-Sung]; Chang, YC[Chang, Young-Chae]
- Issue Date
- 18-Mar-2011
- Citation
- BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, v.406, no.3, pp.353 - 358
- Indexed
- SCIE
SCOPUS
- Journal Title
- BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
- Volume
- 406
- Number
- 3
- Start Page
- 353
- End Page
- 358
- URI
- https://scholarworks.bwise.kr/skku/handle/2021.sw.skku/70519
- DOI
- 10.1016/j.bbrc.2011.02.043
- ISSN
- 0006-291X
- Abstract
- Chemopreventive or anticancer agents induce cancer cells to apoptosis through the activation of adenosine AMP-activated protein kinase (AMPK), which plays a major role as energy sensors under ATP-deprived condition or ROS generation. In this study, we compared the effects of ascochlorin (ASC), from the fungus Ascochyta viciae, and its derivatives on AMPK activity. We also examined a regulatory mechanism for hypoxia-inducible factor-1 alpha (HIF-1 alpha) stabilization in response to 4-O-methylascochlorin (MAC). We found that AMPK activation was mainly involved with MAC, but not ASC and 4-O-carboxymethylascochlorin (AS-6), indicating that the substitution of 4-O-methyl group from 4-O-hydroxyl group of ASC is important in the activation of AMPK and the expression of HIF-1 alpha. MAC-stabilized HIF-1 alpha via AMPK activation triggered by lowering the intracellular ATP level, not by ROS generation, increases glucose uptake and the expression of vascular endothelial growth factor (VEGF) and glucose transporter 1 (GLUT-1), major target genes of HIF-1 alpha. moreover, MAC-induced AMPK activity suppressed survival factors, including mTOR and ERK1/2 or translational regulators, including p70S6K and 4E-BP1. Our data suggest that AMPK is a key determinant of MAC-induced HIF-1 alpha expression in response to energy stress, further implying its involvement in MAC-induced apoptosis. (C) 2011 Elsevier Inc. All rights reserved.
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Collections - Science > Department of Biological Science > 1. Journal Articles
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