Role of HMGB1 in propofol protection of rat intestinal epithelial cells injured by heat shock.
Gut-derived endotoxin and pathogenic bacteria may be important causative factors of morbidity and death during heat stroke. However, as the key component of intestinal mucosal barrier, the molecular mechanism of how intestinal epithelial cells are injured by heat shock is remains unclear. After rat intestinal epithelial cells (IEC-6) had been exposed to heat shock, their viability was measured. Propofol, which plays an important role in anti-inflammation and organ protection, was investigated to see how it affected viability under this stress. Changes of high mobility group box 1 (HMGB1) in IEC-6 cells were measured with RT-PCR and Western blot assay at transcription and translational levels, respectively. Ethyl pyruvate (EP), a specific inhibitor of HMGB1 that can inhibit the release of HMGB1 without affecting its intracellular synthesis, was also investigated. Heat shock significantly reduced the intracellular level of HMGB1, and propofol inhibit its reduction. Propofol protected the heat shock-injured cells, at least partly through inhibiting the release of intracellular HMGB1 to reduce the direct or indirect cell damage caused by HMGB1. Pretreatment with high concentrations of EP also attenuated heat-shock injury.
Department of Anesthesia, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
Jing
J
Tang
Peng
P
Deng
Yu
Y
Jiang
Youqing
Y
Tang
Bin
B
Chen
Lei
L
Su
Zhifeng
Z
Liu
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival; D019610:Cytoprotection; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D024243:HMGB1 Protein / Q000502:physiology*; D018883:Heat Stroke / Q000378:metabolism; D018869:Heat-Shock Response; D007413:Intestinal Mucosa / Q000378:metabolism*; D015742:Propofol / Q000494:pharmacology*; D011773:Pyruvates / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats
D000893:Anti-Inflammatory Agents; D024243:HMGB1 Protein; C104200:Hbp1 protein, rat; D011773:Pyruvates; D012333:RNA, Messenger; C046522:ethyl pyruvate; D015742:Propofol