Circulating hormone adrenomedullin and its binding protein protect neural cells from hypoxia-induced apoptosis

Stephanie M. Wang, Weng Lang Yang

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Background: Brain ischemia is the underlying cause of neuron death during stroke and brain trauma. Neural cells exposed to ischemia can undergo apoptosis. Adrenomedullin (AM) in combination with its enhancing binding protein, AMBP-1, has been shown to reduce tissue damage in inflammation. Methods: To evaluate a beneficial effect of AM/AMBP-1 administration in brain ischemia, we employed an in vitro model of neuronal hypoxia using differentiated human neuroblastoma SH-SY5Y cells. Results: After exposure to 1% O2 for 20 h, neural cells were injured with decreased ATP levels and increased LDH release. Pre-administration of AM/AMBP-1 significantly reduced hypoxia-induced cell injury. Moreover, AM/AMBP-1 treatment reduced the number of TUNEL-positive cells and activation of caspase-3, compared to cells exposed to hypoxia alone. AM/AMBP-1 prevented a reduction of cAMP levels and protein kinase A (PKA) activity in neural cells after hypoxia exposure. Correspondingly, an elevation of cAMP levels by forskolin protected neural cells from hypoxia-induced injury. Inhibition of PKA by KT5720 abolished the protective effect of AM/AMBP-1 on hypoxia-induced apoptosis. Conclusions: AM/AMBP-1 elevates cAMP levels, followed by activating PKA, to protect neural cells from the injury caused by hypoxia. General significance: AM/AMBP-1 may be used as therapeutic agents to prevent neuron damage from brain ischemia.

Original languageEnglish (US)
Pages (from-to)361-367
Number of pages7
JournalBiochimica et Biophysica Acta - General Subjects
Volume1790
Issue number5
DOIs
StatePublished - May 2009
Externally publishedYes

Keywords

  • Adrenomedullin
  • Adrenomedullin binding protein-1
  • Apoptosis
  • cAMP
  • Hypoxia
  • Neural cell
  • Protein kinase A

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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