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S-Nitrosoglutathione (SNOG) Accumulates Hypoxia Inducible Factor-1α in Main Pulmonary Artery Endothelial Cells but not in Micro Pulmonary Vessel Endothelial Cells

  • S. FUJIUCHI
  • Y. YAMAZAKI
  • Y. FUJITA
  • Y. NISHIGAKI
  • A. TAKED
  • Y. YAMAMOTO
  • T. FIJIKANE
  • T. SHIMIZU
  • S. OSANAI
  • T. TAKAHASHI
  • K. KIKUCHI
Conference paper
Part of the ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY book series (AEMB, volume 580)

Abstract

Adequate cellular oxygen tension is essential for maintaining a variety of physiological process. Disorder of oxygen delivery eventually leads to the cell dysfunction. Therefore, sensing mechanism of cellular hypoxia is critical. Under hypoxic condition, a lot of protein is induced in mammalian cells for preventing hypoxic stress. Hypoxia inducible factor-1 (HIF-1) is a transcription factor protein that thought to be a one of the key molecule as gatekeeper of cellular hypoxia. HIF-1 regulates the expression of series of genes involved in angiogenesis, oxygen transport and glucose metabolism (1, 2). Most of these gene products utilize for the maintaining O2 homeostasis. HIF-1 is composed of two subunit called HIF-1α and HIF1β (3). In normoxic and hypoxic condition, HIF-1α and HIF1β mRNA are constitutively expressed (4). With regard to the protein level, HIF-1α is hydroxylated at Pro402 and Pro564 by the enzyme designated prolyl hydroxylase domain containing protein (PHD) under normoxia (5, 6). Hydroxylated HIF-1α binds to the von Hippel Lindau protein (pVHL), which is the substrate for ubiquitin ligase complex (7). Therefore, HIF-1α is rapidly degraded under normoxia by the ubiquitin-protease pathway (8, 9, 10). When cells are exposed to hypoxia, HIF-1α protein escapes from this degradation system. Subsequently, accumulated HIF-1α protein translocates to the nucleus, and dimerizes with HIF-1β 11). This heterodimeric protein binds to hypoxia-responsive element (HRE) and induces transcription of downstream genes (12). Thus, transcriptional activity of HIF-1 is primarily dependent on the HIF-1α expression.

Keywords

Nitric Oxide Nitric Oxide Primary Pulmonary Hypertension Vascular Endothelial Growth Factor Gene Pulmonary Artery Endothelial Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer 2006

Authors and Affiliations

  • S. FUJIUCHI
    • 1
  • Y. YAMAZAKI
    • 1
  • Y. FUJITA
    • 1
  • Y. NISHIGAKI
    • 1
  • A. TAKED
    • 1
  • Y. YAMAMOTO
    • 1
  • T. FIJIKANE
    • 1
  • T. SHIMIZU
    • 1
  • S. OSANAI
    • 2
  • T. TAKAHASHI
    • 2
  • K. KIKUCHI
    • 2
  1. 1.Department of Clinical Research, National Hospital OrganizationDohoku National HospitalAsahikawaJapan
  2. 2.The first department of internal medicineAsahikawa Medical College.Asahikawa

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