title: Polyamine depletion attenuates isoproterenol-induced hypertrophy and endoplasmic reticulum stress in cardiomyocytes.
abstract: OBJECTIVE
  Polyamines (putrescine, spermidine and spermine) play an essential role in cell growth, differentiation and apoptosis. Hypertrophy is accompanied by an increase in polyamine synthesis and endoplasmic reticulum stress (ERS) in cardiomyocytes. The present study was undertaken to elucidate the molecular interactions between polyamines, ERS and cardiac hypertrophy.
  
  
  METHODS
  Myocardial hypertrophy was simulated by incubating cultured neonatal rat cardiomyocytes in 100 nM isoproterenol (ISO). Polyamine deletion was achieved using 0.5 mM difluoromethylornithine (DFMO). Hypertrophy was estimated using cell surface area measurements, total protein concentrations and atrial natriuretic peptide (ANP) gene expression. Apoptosis was measured using flow cytometry and transmission electron microscopy. Expression of ornithine decarboxylase (ODC) and spermidine/spermine N1-acetyltransferase (SSAT) were analyzed via real-time PCR and Western blotting. Protein expression of ERS and apoptosis factors were analyzed using Western blotting.
  
  
  RESULTS
  DFMO (0.5 mM and 2 mM) treatments significantly attenuated hypertrophy and apoptosis induced by ISO in cardiomyocytes. DFMO also decreased lactate dehydrogenase (LDH) and malondialdehyde (MDA) level in the culture medium. In addition, DFMO (0.5 mM) down regulated the expression of ODC, glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), cleaved caspase-12, and Bax and up regulated the expression of SSAT and Bcl-2. Finally, these changes were partly reversed by the addition of exogenous putrescine (0.5 mM).
  
  
  CONCLUSIONS
  The data presented here suggest that polyamine depletion could inhibit cardiac hypertrophy and apoptosis, which is closely related to the ERS pathway.
authors.affiliation: Institute of medicine, Qiqihar Medical University, Qiqihar, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Lin
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Zhang
authors.forename: Lina
authors.initials: L
authors.lastname: Wang
authors.forename: Yajun
authors.initials: Y
authors.lastname: Zhao
authors.forename: Hongzhu
authors.initials: H
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Xiao
authors.forename: Changqing
authors.initials: C
authors.lastname: Xu
authors.forename: Jicheng
authors.initials: J
authors.lastname: Liu
mesh_terms: D000123:Acetyltransferases / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D009320:Atrial Natriuretic Factor / Q000378:metabolism; D006332:Cardiomegaly / Q000139:chemically induced* / Q000378:metabolism*; D053454:Caspase 12 / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects / Q000502:physiology*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009955:Ornithine Decarboxylase / Q000378:metabolism; D011073:Polyamines / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011700:Putrescine / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013095:Spermidine / Q000378:metabolism; D013096:Spermine / Q000378:metabolism; D051742:Transcription Factor CHOP / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D000099228:Diamine N-Acetyltransferase
chemical_list: D000123:Acetyltransferases; D009320:Atrial Natriuretic Factor; D053454:Caspase 12; D018840:HSP70 Heat-Shock Proteins; D007545:Isoproterenol; D007770:L-Lactate Dehydrogenase; D008565:Membrane Proteins; D009955:Ornithine Decarboxylase; D011073:Polyamines; D019253:Proto-Oncogene Proteins c-bcl-2; D011700:Putrescine; D013095:Spermidine; D013096:Spermine; D051742:Transcription Factor CHOP; D051028:bcl-2-Associated X Protein; D000099228:Diamine N-Acetyltransferase; C497251:Ddit3 protein, rat; C018551:glucose-regulated proteins