HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Differential profile of Nix upregulation and translocation during hypoxia/ischaemia in vivo versus in vitro.

Abstract
Nix, a hypoxia-sensitive member of the Bcl-2 family, is upregulated at the mRNA level during hypoxia through induction of a hypoxia-inducible factor-1 alpha (HIF-1 alpha) response element in its promoter sequence. However, the mechanism(s) regulating Nix protein activation remain unclear. The present studies examine Nix protein expression and subcellular distribution in response to hypoxic stimuli in vivo and in culture and to two disparate apoptotic stimuli in vitro. Upregulation and translocation of Nix (by day 5) in hypoxic/serum-deprived CHO-K1 cells, was preceded by Bax activation (by day 4) and caspase-3 processing (by day 2), suggesting that initiation of cell death in vitro is a Nix-independent event. In contrast, an early Nix response (upregulation and translocation to the mitochondria) was observed after 6 h of middle cerebral artery occlusion in the rat. Nix translocation was observed in the ipsilateral cortex and striatum before other histological (infarct development, neuronal loss, apoptotic body formation) or biochemical (Bax activation or caspase-3 cleavage) markers of damage were detected. While fundamental differences between hypoxia/ischaemia in culture and in vivo likely explain the different temporal profiles of Nix, Bax, and caspase-3 activation observed, these studies show that like Bax, mitochondrial accumulation is a common event during Nix activation. These are the first studies to show upregulation and translocation of Nix in the ischaemic brain and suggest Nix to be a novel therapeutic target in ischaemic research. Moreover, Nix upregulation in staurosporine-treated SH-SY5Y cells and dexamethasone-treated A1.1 cells supports a more generalized role for Nix in apoptotic cell death.
AuthorsJui-Lee A Birse-Archbold, Lorraine E Kerr, Paul A Jones, James McCulloch, John Sharkey
JournalJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism (J Cereb Blood Flow Metab) Vol. 25 Issue 10 Pg. 1356-65 (Oct 2005) ISSN: 0271-678X [Print] United States
PMID15902200 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • BNIP3L protein, rat
  • Membrane Proteins
  • Proto-Oncogene Proteins
  • Casp3 protein, rat
  • Caspase 3
  • Caspases
Topics
  • Animals
  • Apoptosis
  • CHO Cells
  • Caspase 3
  • Caspases (metabolism)
  • Cricetinae
  • Hypoxia-Ischemia, Brain (metabolism)
  • Infarction, Middle Cerebral Artery
  • Male
  • Membrane Proteins (analysis, genetics, metabolism)
  • Protein Transport
  • Proto-Oncogene Proteins (analysis, genetics, metabolism)
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors
  • Up-Regulation (genetics)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: