Adrenomedullin binding protein-1 is downregulated during polymicrobial sepsis in the rat.
We have previously shown that administration of adrenomedullin (AM) and AM binding protein-1 (AMBP-1) in combination maintains cardiovascular stability and reduces mortality in a rat model of sepsis. However, it is unknown whether AMBP-1 is reduced under the septic condition and, if so, whether lipopolysaccharide (LPS) plays a role in down-regulating AMBP-1. To determine this, male adult Sprague-Dawley rats were subjected to either polymicrobial sepsis by cecal ligation and puncture (CLP), or endotoxemia by intraperitoneal injection of LPS (15 mg/kg body weight). In an additional group of animals, LPS neutralizing agent polymyxin B (PMB) was given intramuscularly at 0.5 h before and 9 h after CLP. At 20 h after CLP (i.e. the late stage of sepsis) or endotoxemia, hepatic tissue and blood samples were collected. Hepatic AMBP-1 gene expression along with hepatic and plasma AMBP-1 protein levels were measured by RT-PCR and Western blot analysis, respectively. Our results showed that hepatic AMBP-1 gene expression decreased by 65%, hepatic AMBP-1 protein levels decreased by 72%, and plasma levels of AMBP-1 decreased by 59% at 20 h after CLP. Similar results were also seen in the animals receiving LPS injection. Administration of PMB, however, prevented the downregulation of AMBP-1 expression at 20 h after CLP. Thus, AMBP-1 is downregulated in the late phase of sepsis, and LPS plays a critical role in the reduction of AMBP-1.
Cui
Yingjie
Y
Department of Surgery, North Shore University Hospital and Long Island Jewish Medical Center, Manhasset, NY 11030, USA.
Ji
Youxin
Y
Wu
Rongqian
R
Zhou
Mian
M
Wang
Ping
P
D000818:Animals; D015153:Blotting, Western; D002432:Cecum / Q000601:surgery; D017242:Complement Factor H / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D019446:Endotoxemia / Q000097:blood* / Q000139:chemically induced; D015870:Gene Expression / Q000187:drug effects; D008026:Ligation / Q000009:adverse effects; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018805:Sepsis / Q000097:blood* / Q000209:etiology
D008070:Lipopolysaccharides; D012333:RNA, Messenger; C481978:adrenomedullin-binding protein 1, rat; D017242:Complement Factor H