title: Circulating hormone adrenomedullin and its binding protein protect neural cells from hypoxia-induced apoptosis.
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% O(2) 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.
  
  
  CONCLUSIONS
  AM/AMBP-1 may be used as therapeutic agents to prevent neuron damage from brain ischemia.
authors.affiliation: The Feinstein Institute for Medical Research, Manhasset, NY 11030, USA.
authors.forename: Stephanie M
authors.initials: SM
authors.lastname: Wang
authors.forename: Weng-Lang
authors.initials: WL
authors.lastname: Yang
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D053607:Adrenomedullin / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D015687:Cell Hypoxia / Q000187:drug effects; D045744:Cell Line, Tumor; D005576:Colforsin / Q000494:pharmacology; D017242:Complement Factor H / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D019610:Cytoprotection; D004249:DNA Damage; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008954:Models, Biological; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology
chemical_list: D000255:Adenosine Triphosphate; D053607:Adrenomedullin; D053148:Caspase 3; D005576:Colforsin; D017242:Complement Factor H; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D007770:L-Lactate Dehydrogenase; D047428:Protein Kinase Inhibitors; C493495:CFH protein, human