title: Isoproterenol induced hypertrophy and associated signaling pathways are modulated by somatostatin in H9c2 cells.
abstract: BACKGROUND
  Somatostatin (SST), a growth hormone inhibitory peptide plays key role in regulation of cell proliferation via modulation of mitogen activated protein kinases (MAPKs) and cell survival pathway. In cardiac physiology, β-Adrenergic receptors (β-ARs) play crucial role in regulation of downstream signaling pathways in receptor specific manner. The aim of the current study was to delineate the mechanistic insight for the role of SST on β-AR mediated signaling which promotes hypertrophy and apoptosis in rat fetal cardiomyocytes (H9c2 cells). Accordingly, SST dependent changes in signaling molecules including second messenger cAMP, PKA/CREB as well as MAPKs including ERK and p38 which are key mediators of hypertrophy and apoptosis were analyzed.
  
  
  RESULTS
  In the present study, we determined receptor specific effects on intracellular cAMP levels, signaling by western blot analysis and apoptosis by using JC-1 and Hoechst-33258 staining. Here, we present the data which indicates that SST inhibits isoproterenol induced hypertrophy and apoptosis in H9c2 cells. Importantly, SST inhibits β-ARs agonist induced cAMP activation and SST mediated inhibition of cAMP was enhanced in presence of β-ARs antagonist. SST enhances β2AR agonist formoterol mediated effects on PKA, CREB and ERK1/2 phosphorylations whereas it inhibits isoproterenol mediated ERK1/2 and p38 signaling in concentration dependent manner.
  
  
  CONCLUSIONS
  Taken together, these results presented here provide a novel insight for the potential role of SST in regulation of β-AR mediated effects on hypertrophy and modulation of hypertrophy promoting signaling in H9c2 cells.
authors.affiliation: Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, BC, Canada V6T1Z3.
authors.forename: Rishi K
authors.initials: RK
authors.lastname: Somvanshi
authors.forename: Xiaofan
authors.initials: X
authors.lastname: Qiu
authors.forename: Ujendra
authors.initials: U
authors.lastname: Kumar
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000097:blood / Q000139:chemically induced / Q000473:pathology; D002460:Cell Line; D007545:Isoproterenol / Q000097:blood / Q000494:pharmacology / Q000633:toxicity*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000473:pathology*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D013004:Somatostatin / Q000097:blood / Q000494:pharmacology*
chemical_list: D013004:Somatostatin; D007545:Isoproterenol