NF-κB p65 involves in reperfusion injury and iNOS gene regulation in skeletal muscle

✍ Scribed by Wen-Ning Qi; Pruk Chaiyakit; Yongting Cai; Diane M. Allen; Long-En Chen; Anthony V. Seaber; James R. Urbaniak

• Book ID: 102512607
• Publisher: John Wiley and Sons
• Year: 2004
• Tongue: English
• Weight: 178 KB
• Volume: 24
• Category: Article
• ISSN: 0738-1085
• DOI: 10.1002/micr.20030

✦ Synopsis

This study investigated the effects of inhibition of NF-kappaB activation on microcirculation and inducible NOS expression in reperfused rat cremaster muscle. The muscle from 16 rats underwent 5-h ischemia and 90-min reperfusion. Each rat received NF-kappaB inhibitor pyrrolidine dithiocarbamate (PDTC, 150 mg/kg) or phosphate-buffered saline 15 min before reperfusion. Results showed that PDTC treatment had a significant overall increase in muscle blood flow during reperfusion. Blood flow more rapidly recovered to and over baseline in the PDTC-treated group than in controls, with a significant difference at 10-30 min and 70-90 min. Expression of iNOS mRNA had a 167-fold increase from normal in controls, but was significantly (P < 0.05) reduced to a 63-fold increase in PDTC-treated muscles. In addition, PDTC treatment significantly (P < 0.05) decreased a reperfusion-induced increase in activated NF-kappaB p65 and nuclear p65 protein. Our results suggest that NF-kappaB is involved in I/R injury and that inhibition of NF-kappaB p65 activation affords protection against I/R injury, perhaps via downregulating expression of iNOS transcription.