11
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Identification of a novel hypoxia-inducible factor 1-responsive gene, RTP801, involved in apoptosis.

      Molecular and Cellular Biology

      Amino Acid Sequence, Animals, Anoxia, genetics, Apoptosis, drug effects, Base Sequence, Cell Differentiation, Cloning, Molecular, DNA-Binding Proteins, chemistry, metabolism, Gene Expression Regulation, Humans, Hydrogen Peroxide, pharmacology, Hypoxia-Inducible Factor 1, Hypoxia-Inducible Factor 1, alpha Subunit, In Situ Hybridization, Liposomes, Lung, cytology, Mice, Molecular Sequence Data, Nuclear Proteins, PC12 Cells, RNA, Messenger, Rats, Reactive Oxygen Species, Repressor Proteins, Sequence Homology, Amino Acid, Stroke, Transcription Factors, Tumor Cells, Cultured, Up-Regulation

      Read this article at

      ScienceOpenPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Hypoxia is an important factor that elicits numerous physiological and pathological responses. One of the major gene expression programs triggered by hypoxia is mediated through hypoxia-responsive transcription factor hypoxia-inducible factor 1 (HIF-1). Here, we report the identification and cloning of a novel HIF-1-responsive gene, designated RTP801. Its strong up-regulation by hypoxia was detected both in vitro and in vivo in an animal model of ischemic stroke. When induced from a tetracycline-repressible promoter, RTP801 protected MCF7 and PC12 cells from hypoxia in glucose-free medium and from H(2)O(2)-triggered apoptosis via a dramatic reduction in the generation of reactive oxygen species. However, expression of RTP801 appeared toxic for nondividing neuron-like PC12 cells and increased their sensitivity to ischemic injury and oxidative stress. Liposomal delivery of RTP801 cDNA to mouse lungs also resulted in massive cell death. Thus, the biological effect of RTP801 overexpression depends on the cell context and may be either protecting or detrimental for cells under conditions of oxidative or ischemic stresses. Altogether, the data suggest a complex type of involvement of RTP801 in the pathogenesis of ischemic diseases.

          Related collections

          Author and article information

          Journal
          11884613
          133671

          Comments

          Comment on this article