title: An assessment of norepinephrine mediated hypertrophy to apoptosis transition in cardiac cells: a signal for cell death.
abstract: OBJECTIVE
  Heart is an organ which is under a constant work load that generates numerous stress responses. Heart failure is associated with increased plasma norepinephrine (NE) and hypertrophic cell death. Within the current study we try to understand the concentration dependent molecular switch from hypertrophy to apoptosis under stress.
  
  
  METHODS
  The effect of increasing concentration of NE on cell death was studied using MTT assay based on which further experimental conditions were decided. Trypan Blue staining and TUNEL assay were done at selected concentrations of NE. Cellular and nuclear morphology at these concentrations was studied using Haematoxylin-Eosin, DAPI and PI stains. The molecular switch between hypertrophy and cell death was studied by expression analysis of β-MyHC and TNF-α. Rhodamine and DCFH-DA staining were done to evaluate the role of mitochondria and ROS under these conditions. Role of caspases under these transitions was also evaluated.
  
  
  RESULTS
  NE shows steep falls in cell viability at 50 μM and 100 μM concentrations. The cellular and nuclear morphology is altered at these concentrations along with alterations at molecular level showing a shift from hypertrophy towards cell death. Altered mitochondrial membrane potential and increase in ROS support this which leads to caspase dependent activation of cell death.
  
  
  CONCLUSIONS
  We show that at 50 μM NE, there occurs a transition from cellular hypertrophy towards death. This could be beneficial to prevent hypertrophy induced cardiac cell death and evaluating cardio protective therapeutic targets in vitro.
authors.affiliation: Department of Biotechnology, Jaypee Institute of Information Technology, A-10, Sector-62, Noida 201307, Uttar Pradesh, India.
authors.forename: Aditi
authors.initials: A
authors.lastname: Jain
authors.affiliation: Department of Biotechnology, Jaypee Institute of Information Technology, A-10, Sector-62, Noida 201307, Uttar Pradesh, India.
authors.forename: Neha
authors.initials: N
authors.lastname: Atale
authors.affiliation: Universitatsklinkum, Medical Faculty at Otto Von Guericke University, Magdeburg, Germany.
authors.forename: Shrey
authors.initials: S
authors.lastname: Kohli
authors.affiliation: Department of Biotechnology, Jaypee Institute of Information Technology, A-10, Sector-62, Noida 201307, Uttar Pradesh, India.
authors.forename: Susinjan
authors.initials: S
authors.lastname: Bhattacharya
authors.affiliation: Peptide and Proteomics Division, Defence Institute of Physiology and Allied Sciences (DIPAS), DRDO, Delhi, India.
authors.forename: Manish
authors.initials: M
authors.lastname: Sharma
authors.affiliation: Department of Biotechnology, Jaypee Institute of Information Technology, A-10, Sector-62, Noida 201307, Uttar Pradesh, India. Electronic address: vibha.rani@jiit.ac.in.
authors.forename: Vibha
authors.initials: V
authors.lastname: Rani
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005562:Formazans / Q000032:analysis; D006984:Hypertrophy / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D008856:Microscopy, Fluorescence; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology*; D012313:RNA / Q000737:chemistry / Q000235:genetics; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013778:Tetrazolium Salts / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D024723:Ventricular Myosins / Q000235:genetics / Q000378:metabolism
chemical_list: D005562:Formazans; D013778:Tetrazolium Salts; D014409:Tumor Necrosis Factor-alpha; C079782:MTT formazan; D012313:RNA; D024723:Ventricular Myosins; D009638:Norepinephrine
keywords: Apoptosis; Cardiomyocytes; Hypertrophy; Norepinephrine; Reactive oxygen species; Transition