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Fatty Acid Uptake and Lipid Storage Induced by HIF-1 alpha Contribute to Cell Growth and Survival after Hypoxia-Reoxygenation

Please always quote using this URN: urn:nbn:de:bvb:20-opus-115162
  • An in vivo model of antiangiogenic therapy allowed us to identify genes upregulated by bevacizumab treatment, including Fatty Acid Binding Protein 3 (FABP3) and FABP7, both of which are involved in fatty acid uptake. In vitro, both were induced by hypoxia in a hypoxia-inducible factor-1 alpha (HIF-1 alpha)-dependent manner. There was a significant lipid droplet (LD) accumulation in hypoxia that was time and O-2 concentration dependent. Knockdown of endogenous expression of FABP3, FABP7, or Adipophilin (an essential LD structural component)An in vivo model of antiangiogenic therapy allowed us to identify genes upregulated by bevacizumab treatment, including Fatty Acid Binding Protein 3 (FABP3) and FABP7, both of which are involved in fatty acid uptake. In vitro, both were induced by hypoxia in a hypoxia-inducible factor-1 alpha (HIF-1 alpha)-dependent manner. There was a significant lipid droplet (LD) accumulation in hypoxia that was time and O-2 concentration dependent. Knockdown of endogenous expression of FABP3, FABP7, or Adipophilin (an essential LD structural component) significantly impaired LD formation under hypoxia. We showed that LD accumulation is due to FABP3/7-dependent fatty acid uptake while de novo fatty acid synthesis is repressed in hypoxia. We also showed that ATP production occurs via beta-oxidation or glycogen degradation in a cell-type-dependent manner in hypoxia-reoxygenation. Finally, inhibition of lipid storage reduced protection against reactive oxygen species toxicity, decreased the survival of cells subjected to hypoxia-reoxygenation in vitro, and strongly impaired tumorigenesis in vivo.show moreshow less

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Metadaten
Author: Karim Bensaad, Elena Favaro, Caroline A. Lewis, Barrie Peck, Simon Lord, Jennifer M. Collins, Katherine E. Pinnick, Simon Wigfield, Francesca M. Buffa, Ji-Liang Li, Qifeng Zhang, Michael J. O. Wakelam, Fredrik Karpe, Almut Schulze, Adrian L. Harris
URN:urn:nbn:de:bvb:20-opus-115162
Document Type:Journal article
Faculties:Medizinische Fakultät / Theodor-Boveri-Institut für Biowissenschaften
Language:English
Parent Title (English):Cell Reports
ISSN:2211-1247
Year of Completion:2014
Volume:9
Issue:1
Pagenumber:349-365
Source:Cell Reports 9, 349–365. DOI: 10.1016/j.celrep.2014.08.056
DOI:https://doi.org/10.1016/j.celrep.2014.08.056
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=25263561
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:beta-oxidation; binding protein; cancer cell; complex-III; inducible factor-I; lipogenesis; metabolism; proliferation; resistance; triglyceride accumulation
Release Date:2015/07/11
Licence (German):License LogoCC BY-NC-ND: Creative-Commons-Lizenz: Namensnennung, Nicht kommerziell, Keine Bearbeitung