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

被引:13
作者
Rushing, Gregory D. [1 ]
Britt, L. D. [1 ]
机构
[1] Eastern Virginia Med Sch, Dept Surg, Norfolk, VA 23501 USA
关键词
D O I
10.1016/j.jamcollsurg.2007.01.029
中图分类号
R61 [外科手术学];
学科分类号
摘要
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.
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页码:964 / 967
页数:4
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