PMID- 10728381
OWN - NLM
STAT- MEDLINE
DCOM- 20000413
LR  - 20190513
IS  - 0008-6363 (Print)
IS  - 0008-6363 (Linking)
VI  - 45
IP  - 3
DP  - 2000 Feb
TI  - Tumor necrosis factor-alpha induces apoptosis via inducible nitric oxide synthase 
      in neonatal mouse cardiomyocytes.
PG  - 595-602
AB  - OBJECTIVE: It has been demonstrated that tumor necrosis factor-alpha (TNF alpha) 
      induces apoptosis in cardiac myocytes. However, its mechanism of action is still 
      not well understood. In the present study, we hypothesized that TNF alpha induces 
      myocardial apoptosis by induction of inducible nitric oxide synthase (iNOS). 
      METHODS: Neonatal cardiac myocytes were isolated from iNOS (-/-) mutant and 
      C57BL6 wild type mice. Cells were cultured for 3 days before treatment with an NO 
      donor or TNF alpha. Following treatment with S-nitroso-N-acetyl-penicillamine 
      (SNAP) or TNF-alpha, cells were tested for apoptosis by terminal deoxynucleotidyl 
      transfer-mediated end labeling (TUNEL) staining and cell death detection ELISA. 
      NO production was measured by nitrite concentration in the culture medium. 
      Cardiomyocyte expression of iNOS and TNF type 1 receptor (TNFR1) mRNA was 
      determined by reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: 
      SNAP (0.01-100 microM) induced apoptosis of cardiac myocytes in a 
      concentration-dependent manner in the wild type mice (n = 5, P < 0.01). TNFR1 
      mRNA was expressed in neonatal cardiomyocytes from both wild type and iNOS (-/-) 
      mutant mice. TNF alpha induced a concentration-dependent increase in iNOS mRNA 
      expression and nitrite production as well as significant apoptosis of 
      cardiomyocytes in the wild type mice (n = 4, P < 0.01). However, without iNOS 
      expression, the apoptotic effects of TNF-alpha were significantly attenuated in 
      cardiomyocytes from iNOS (-/-) mutant mice (n = 4, P < 0.05). CONCLUSION: TNF 
      alpha induces apoptosis via iNOS expression and NO production in neonatal mouse 
      cardiomyocytes.
FAU - Song, W
AU  - Song W
AD  - London Health Sciences Centre, Department of Medicine, Ontario, Canada.
FAU - Lu, X
AU  - Lu X
FAU - Feng, Q
AU  - Feng Q
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Cardiovasc Res
JT  - Cardiovascular research
JID - 0077427
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.14.13.39 (Nos2 protein, mouse)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - Animals, Newborn
MH  - Apoptosis/*drug effects
MH  - Cells, Cultured
MH  - DNA Fragmentation
MH  - Enzyme Induction
MH  - In Situ Nick-End Labeling
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Mutant Strains
MH  - Microscopy, Electron
MH  - Myocardium/*metabolism/ultrastructure
MH  - Nitric Oxide/metabolism
MH  - Nitric Oxide Synthase/*biosynthesis/genetics
MH  - Nitric Oxide Synthase Type II
MH  - Receptors, Tumor Necrosis Factor/genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Tumor Necrosis Factor-alpha/*pharmacology
EDAT- 2000/03/23 09:00
MHDA- 2000/04/15 09:00
CRDT- 2000/03/23 09:00
PHST- 2000/03/23 09:00 [pubmed]
PHST- 2000/04/15 09:00 [medline]
PHST- 2000/03/23 09:00 [entrez]
AID - S0008-6363(99)00395-8 [pii]
AID - 10.1016/s0008-6363(99)00395-8 [doi]
PST - ppublish
SO  - Cardiovasc Res. 2000 Feb;45(3):595-602. doi: 10.1016/s0008-6363(99)00395-8.