title: Pharmacological concentrations of irisin increase cell proliferation without influencing markers of neurite outgrowth and synaptogenesis in mouse H19-7 hippocampal cell lines.
abstract: OBJECTIVE
  Irisin is a novel, myocyte secreted, hormone that has been proposed to mediate the beneficial effects of exercise on metabolism. Irisin is expressed, at lower levels, in human brains and knock-down of the precursor of irisin, FNDC5, decreases neural differentiation of mouse embryonic stem cells. No previous studies have evaluated whether irisin may directly regulate hippocampal neurogenesis in mouse hippocampal neuronal (HN) cells.
  
  
  METHODS
  Hippocampal neurogenesis and irisin signaling were studied in vitro using mouse H19-7 HN cell lines.
  
  
  RESULTS
  We observed that cell proliferation is regulated by irisin in a dose-dependent manner in mouse H19-7 HN cells. Specifically, physiological concentrations of irisin, 5 to 10nmol/L, had no effect on cell proliferation when compared to control. By contrast, pharmacological concentrations of irisin, 50 to 100nmol/L, increased cell proliferation when compared to control. Similar to these results regarding irisin's effects on cell proliferation, we also observed that only pharmacological concentrations of irisin increased STAT3, but not AMPK and/or ERK, activation. Finally, we observed that irisin did not activate either microtubule-associated protein 2, a specific neurite outgrowth marker, or Synapsin, a specific synaptogenesis marker in mouse H19-7 HN cells.
  
  
  CONCLUSIONS
  Our data suggest that irisin, in pharmacological concentrations, increases cell proliferation in mouse H19-7 HN cells via STAT3, but not AMPK and/or ERK, signaling pathways. By contrast, neither physiological nor pharmacological concentrations of irisin alter markers of hippocampal neurogenesis in mouse H19-7 HN cell lines.
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. hmoon@bidmc.harvard.edu.
authors.forename: Hyun-Seuk
authors.initials: HS
authors.lastname: Moon
authors.forename: Fadime
authors.initials: F
authors.lastname: Dincer
authors.forename: Christos S
authors.initials: CS
authors.lastname: Mantzoros
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D005353:Fibronectins / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D016501:Neurites / Q000187:drug effects*; D055495:Neurogenesis / Q000187:drug effects*; D011494:Protein Kinases / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology; D050796:STAT3 Transcription Factor / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D013569:Synapses / Q000187:drug effects*
chemical_list: C577593:FNDC5 protein, human; D005353:Fibronectins; D011994:Recombinant Proteins; D050796:STAT3 Transcription Factor; D011494:Protein Kinases; D000091162:AMP-Activated Protein Kinase Kinases
keywords: AMP-activated protein kinase; AMPK; ERK; Extracellular signal-regulated kinase; HN; Hippocampal neurogenesis; Hippocampal neuronal cells; Irisin; MAP2; Microtubule-associated protein 2; STAT3; Signal transducer and activator of transcription 3; Signaling