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


METHODS
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.
Rushing
Gregory D
GD
Department of Surgery, Eastern Virginia Medical School, Norfolk, VA, USA.
Britt
L D
LD
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D016227:Benzoquinones / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D048031:JNK Mitogen-Activated Protein Kinases / Q000097:blood*; D047029:Lactams, Macrocyclic / Q000494:pharmacology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000097:blood / Q000503:physiopathology*; D017828:Rifabutin / Q000031:analogs & derivatives; D018709:Statistics, Nonparametric; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D016227:Benzoquinones; D004791:Enzyme Inhibitors; D047029:Lactams, Macrocyclic; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D017828:Rifabutin; C020754:herbimycin; D048031:JNK Mitogen-Activated Protein Kinases