Inhibition of NF-KB does not induce c-Jun N-terminal kinase-mediated apoptosis in reperfusion injury

J Am Coll Surg. 2007 May;204(5):964-7; discussion 967-8. doi: 10.1016/j.jamcollsurg.2007.01.029.


Background: The role of C-Jun N-terminal Kinase (c-Jun Kinase) in apoptosis is unclear. It is likely that c-Jun Kinase activation is cell type and stimulus dependent. c-Jun Kinase promotes tumor necrosis factor (TNF)-alpha mediated apoptosis in nuclear factor (NF)-KB deficient cells. Minimal NF-KB expression may be enough to abrogate c-Jun Kinase-mediated apoptosis during reperfusion injury.

Study design: Forty Sprague-Dawley rats underwent hemorrhagic ischemia and reperfusion. Twenty experimental animals were treated with the NF-KB inhibitor herbimycin A, and 20 control animals underwent only hemorrhage and reperfusion. Serum TNF-alpha and c-Jun Kinase levels were measured. Adrenal, kidney, liver, ileum, colon, and skeletal muscle tissues were evaluated for apoptosis by hematoxylin and eosin staining.

Results: TNF-alpha levels were 400 pg/mL (control) and 385 pg/mL (experimental) during ischemia (p=0.46), increased in controls to 450 pg/mL, and decreased in the experimental arm to 175 pg/mL (p=0.028). c-Jun Kinase levels were 1,525 pg/mL (control) and 1,475 pg/mL (experimental) during ischemia (p=0.35) and increased to 5,250 pg/mL (control) and 5,000 pg/mL (experimental) after reperfusion (p=0.26). In control animals, necrosis was seen in kidney, adrenal, and liver specimens. Compared with controls, experimental animals had average tissue hemorrhage scores of less than 1 (p < 0.001), with no necrosis seen in any experimental arm (p<0.001).

Conclusions: During inhibition of NF-KB, c-Jun Kinase levels remained unchanged. But no increase in cell death or necrosis was seen in tissue samples. Antiapoptotic effects were unchanged with the down-regulation of NF-KB. Minimal expression of NF-KB may be enough to protect against apoptosis in reperfusion injury.

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Benzoquinones / pharmacology*
  • Enzyme Inhibitors / pharmacology*
  • Female
  • JNK Mitogen-Activated Protein Kinases / blood*
  • Lactams, Macrocyclic / pharmacology*
  • NF-kappa B / antagonists & inhibitors*
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury / blood
  • Reperfusion Injury / physiopathology*
  • Rifabutin / analogs & derivatives
  • Statistics, Nonparametric
  • Tumor Necrosis Factor-alpha / blood


  • Benzoquinones
  • Enzyme Inhibitors
  • Lactams, Macrocyclic
  • NF-kappa B
  • Tumor Necrosis Factor-alpha
  • Rifabutin
  • herbimycin
  • JNK Mitogen-Activated Protein Kinases