NF-kappaB p65 involves in reperfusion injury and iNOS gene regulation in skeletal muscle.
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.
Orthopaedic Research Laboratories, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
Wen-Ning
WN
Qi
Pruk
P
Chaiyakit
Yongting
Y
Cai
Diane M
DM
Allen
Long-En
LE
Chen
Anthony V
AV
Seaber
James R
JR
Urbaniak
D000818:Animals; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D008833:Microcirculation / Q000502:physiology*; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000187:drug effects; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D011759:Pyrrolidines / Q000494:pharmacology*; D012333:RNA, Messenger; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy*; D013859:Thiocarbamates / Q000494:pharmacology*; D051996:Transcription Factor RelA
D016328:NF-kappa B; D011759:Pyrrolidines; D012333:RNA, Messenger; D013859:Thiocarbamates; D051996:Transcription Factor RelA; C020972:pyrrolidine dithiocarbamic acid; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat