title: Hypoxic preconditioning induces neuroprotective stanniocalcin-1 in brain via IL-6 signaling.
abstract: OBJECTIVE
  Exposure of animals for a few hours to moderate hypoxia confers relative protection against subsequent ischemic brain damage. This phenomenon, known as hypoxic preconditioning, depends on new RNA and protein synthesis, but its molecular mechanisms are poorly understood. Increased expression of IL-6 is evident, particularly in the lungs of animals subjected to hypoxic preconditioning. Stanniocalcin-1 (STC-1) is a 56-kDa homodimeric glycoprotein originally discovered in bony fish, where it regulates calcium/phosphate homeostasis and protects against toxic hypercalcemia. We originally reported expression of mammalian STC-1 in brain neurons and showed that STC-1 guards neurons against hypercalcemic and hypoxic damage.
  
  
  METHODS
  We treated neural Paju cells with IL-6 and measured the induction of STC-1 mRNA. In addition, we quantified the effect of hypoxic preconditioning on Stc-1 mRNA levels in brains of wild-type and IL-6 deficient mice. Furthermore, we monitored the Stc-1 response in brains of wild-type and transgenic mice, overexpressing IL-6 in the astroglia, before and after induced brain injury.
  
  
  RESULTS
  Hypoxic preconditioning induced an upregulated expression of Stc-1 in brains of wild-type but not of IL-6-deficient mice. Induced brain injury elicited a stronger STC-1 response in brains of transgenic mice, with targeted astroglial IL-6 expression, than in brains of wild-type mice. Moreover, IL-6 induced STC-1 expression via MAPK signaling in neural Paju cells.
  
  
  CONCLUSIONS
  These findings indicate that IL-6-mediated expression of STC-1 is one molecular mechanism of hypoxic preconditioning-induced tolerance to brain ischemia.
authors.affiliation: Department of Pathology, Haartman Institute, University of Helsinki, Helsinki, Finland.
authors.forename: Johan A
authors.initials: JA
authors.lastname: Westberg
authors.forename: Martina
authors.initials: M
authors.lastname: Serlachius
authors.forename: Petri
authors.initials: P
authors.lastname: Lankila
authors.forename: Milena
authors.initials: M
authors.lastname: Penkowa
authors.forename: Juan
authors.initials: J
authors.lastname: Hidalgo
authors.forename: Leif C
authors.initials: LC
authors.lastname: Andersson
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D006023:Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control; D015850:Interleukin-6 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D019194:Ischemic Preconditioning / Q000379:methods*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018696:Neuroprotective Agents / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D006023:Glycoproteins; D015850:Interleukin-6; D018696:Neuroprotective Agents; C051795:teleocalcin