PMID- 10870332
OWN - NLM
STAT- MEDLINE
DCOM- 20000714
LR  - 20161013
IS  - 0929-6646 (Print)
IS  - 0929-6646 (Linking)
VI  - 99
IP  - 5
DP  - 2000 May
TI  - Effects of norepinephrine on apoptosis in rat neonatal cardiomyocytes.
PG  - 412-8
AB  - BACKGROUND AND PURPOSE: Norepinephrine (NE) is elevated in heart failure and can 
      induce apoptosis in adult cardiac myocytes. However, it is not known whether NE 
      can induce apoptosis in neonatal cardiac myocytes. This study examined the 
      ability of NE to stimulate apoptosis in rat neonatal cardiac myocytes in vitro. 
      METHODS: Neonatal rat cardiac myocytes were exposed to NE alone, NE + 
      propranolol, or NE + prazosin for 24 hours. Apoptosis was assayed by DNA 
      laddering with agarose gel electrophoresis and immunofluorescent terminal 
      deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. 
      Reverse transcription polymerase chain reaction was used to evaluate the 
      expression of Mcl-1. Creatine kinase activity in the cultured medium was used as 
      a measure of the toxicity of NE on myocytes. RESULTS: NE increased DNA laddering 
      on agarose gel electrophoresis and increased the number of apoptotic cells in a 
      dose-dependent manner. No increase in apoptosis was found in response to NE doses 
      between 1 and 50 mumol/L. NE at concentrations of 100 to 400 mumol/L increased 
      apoptosis from 10% to 31% of cells. The ability of NE to stimulate apoptosis in 
      rat neonatal cardiac myocytes was completely blocked by propranolol, but not 
      prazosin. NE treatment at high concentrations sharply reduced the level of Mcl-1 
      mRNA, coincident with the increase in the number of apoptotic cells. Creatine 
      kinase activity in the cultured medium was similar among the controls and 
      NE-treated myocytes. CONCLUSIONS: Our results showed that NE at high 
      concentrations stimulated apoptosis in rat neonatal cardiac myocytes in vitro. 
      Apoptosis induced by NE was associated with down-regulation of Mcl-1. However, NE 
      at the same concentration was not toxic to rat neonatal cardiac myocytes.
FAU - Shyu, K G
AU  - Shyu KG
AD  - Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, 
      Taiwan.
FAU - Kuan, P
AU  - Kuan P
FAU - Chang, M L
AU  - Chang ML
FAU - Wang, B W
AU  - Wang BW
FAU - Huang, F Y
AU  - Huang FY
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Singapore
TA  - J Formos Med Assoc
JT  - Journal of the Formosan Medical Association = Taiwan yi zhi
JID - 9214933
RN  - 0 (Myeloid Cell Leukemia Sequence 1 Protein)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - EC 2.7.3.2 (Creatine Kinase)
RN  - X4W3ENH1CV (Norepinephrine)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Apoptosis/*drug effects
MH  - Creatine Kinase/metabolism
MH  - DNA Fragmentation
MH  - Dose-Response Relationship, Drug
MH  - Heart/*drug effects
MH  - Myeloid Cell Leukemia Sequence 1 Protein
MH  - Myocardium/cytology
MH  - Neoplasm Proteins/genetics
MH  - Norepinephrine/*pharmacology
MH  - *Proto-Oncogene Proteins c-bcl-2
MH  - Rats
MH  - Rats, Wistar
EDAT- 2000/06/28 11:00
MHDA- 2000/07/25 11:00
CRDT- 2000/06/28 11:00
PHST- 2000/06/28 11:00 [pubmed]
PHST- 2000/07/25 11:00 [medline]
PHST- 2000/06/28 11:00 [entrez]
PST - ppublish
SO  - J Formos Med Assoc. 2000 May;99(5):412-8.