PMID- 10533621
OWN - NLM
STAT- MEDLINE
DCOM- 19991124
LR  - 20190513
IS  - 0008-6363 (Print)
IS  - 0008-6363 (Linking)
VI  - 42
IP  - 3
DP  - 1999 Jun
TI  - Tumor necrosis factor-alpha enhances hypoxia-reoxygenation-mediated apoptosis in 
      cultured human coronary artery endothelial cells: critical role of protein kinase 
      C.
PG  - 805-13
AB  - BACKGROUND: Ischemia and tumor necrosis factor-alpha (TNF alpha) released during 
      ischemia both cause apoptosis and necrosis of myocardial tissues. Since 
      endothelium may be critically important in determination of cardiac function, we 
      examined the interaction between TNF alpha and hypoxia-reoxygenation with regard 
      to induction of apoptosis and underlying signaling pathway in cultured human 
      coronary artery endothelial cells (HCAECs). METHODS AND RESULTS: HCAECs were 
      cultured and exposed to hypoxia alone, hypoxia-reoxygenation, TNF alpha alone, 
      TNF alpha plus hypoxia-reoxygenation, or TNF alpha only during the period of 
      reoxygenation. Apoptosis was evaluated by transmission electron microscopy, DNA 
      nick-end labeling and DNA laddering. Hypoxia alone caused modest time-dependent 
      apoptosis of cultured HCAECs, and reoxygenation increased the number of apoptotic 
      cells (P < 0.01 vs. hypoxia alone). TNF alpha induced concentration-dependent 
      apoptosis, and enhanced reoxygenation-mediated apoptosis in cultured HCAECs (P < 
      0.01 vs. hypoxia-reoxygenation alone). As expected, monoclonal antibody to TNF 
      alpha significantly blocked the pro-apoptotic effect of TNF alpha-induced 
      apoptosis (P < 0.01). TNF alpha-induced apoptosis was found to be associated with 
      marked activation of protein kinase C (PKC), and pretreatment of cells with a 
      specific PKC inhibitor markedly reduced TNF alpha-mediated PKC activity and 
      apoptosis. CONCLUSION: These observations indicate that hypoxia alone causes 
      modest apoptosis, reoxygenation increases apoptosis beyond that caused by hypoxia 
      in cultured HCAECs. TNF alpha alone causes apoptosis, and further enhances 
      apoptosis caused by hypoxia-reoxygenation. The activation of PKC plays a critical 
      role in TNF alpha-induced apoptosis of cultured HCAECs.
FAU - Li, D
AU  - Li D
AD  - Department of Medicine, University of Florida College of Medicine, Gainesville 
      32610, USA.
FAU - Yang, B
AU  - Yang B
FAU - Mehta, J L
AU  - Mehta JL
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - England
TA  - Cardiovasc Res
JT  - Cardiovascular research
JID - 0077427
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.7.11.13 (Protein Kinase C)
SB  - IM
MH  - Antibodies, Monoclonal/pharmacology
MH  - Apoptosis/*drug effects
MH  - Cell Hypoxia
MH  - Cells, Cultured
MH  - Coronary Vessels
MH  - Endothelium, Vascular/enzymology/pathology/*physiopathology
MH  - Enzyme Activation
MH  - Humans
MH  - Microscopy, Electron
MH  - Myocardial Reperfusion Injury/enzymology/pathology/*physiopathology
MH  - Protein Kinase C/antagonists & inhibitors/metabolism
MH  - *Signal Transduction
MH  - Tumor Necrosis Factor-alpha/immunology/*pharmacology
EDAT- 1999/10/26 00:00
MHDA- 1999/10/26 00:01
CRDT- 1999/10/26 00:00
PHST- 1999/10/26 00:00 [pubmed]
PHST- 1999/10/26 00:01 [medline]
PHST- 1999/10/26 00:00 [entrez]
AID - S0008636398003423 [pii]
AID - 10.1016/s0008-6363(98)00342-3 [doi]
PST - ppublish
SO  - Cardiovasc Res. 1999 Jun;42(3):805-13. doi: 10.1016/s0008-6363(98)00342-3.