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10.1007/s00011-014-0747-z

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C4158117!4158117!24915805
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suck abstract from ncbi


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pmid24915805      Inflamm+Res 2014 ; 63 (9): 741-56
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  • Effects of 5,14-HEDGE, a 20-HETE mimetic, on lipopolysaccharide-induced changes in MyD88/TAK1/IKK?/I?B-?/NF-?B pathway and circulating miR-150, miR-223, and miR-297 levels in a rat model of septic shock #MMPMID24915805
  • Sari AN; Korkmaz B; Serin MS; Kacan M; Unsal D; Buharalioglu CK; Firat SS; Manhati VL; Falck JR; Malik KU; Tunctan B
  • Inflamm Res 2014[Sep]; 63 (9): 741-56 PMID24915805show ga
  • Objectives: We have previously demonstrated that a stable synthetic analog of 20-hydroxyeicosatetraenoic acid (20-HETE), N-(20-hydroxyeicosa-5[Z],14[Z]-dienoyl)glycine (5,14-HEDGE), which mimics the effects of endogenously produced 20-HETE, prevents vascular hyporeactivity, hypotension, tachycardia, inflammation, and mortality in a rodent model of septic shock. The present study was performed to determine whether decreased renal and cardiovascular expression and activity of myeloid differentiation factor 88 (MyD88)/transforming growth factor-activated kinase 1 (TAK1)/inhibitor of ?B (I?B) kinase ? (IKK?)/I?B-?/nuclear factor-?B (NF-?B) pathway and reduced circulating microRNA (miR)-150, miR-223, and miR-297 expression levels participate in the protective effect of 5,14-HEDGE against hypotension, tachycardia, and inflammation in response to systemic administration of lipopolysaccharide (LPS). Methods: Conscious male Wistar rats received saline (4 ml/kg) or LPS (10 mg/kg) at time 0. Blood pressure and heart rate were measured using a tail-cuff device. Separate groups of LPS-treated rats were given 5,14-HEDGE (30 mg/kg) 1 h after injection of saline or LPS. The rats were sacrificed 4 h after LPS challenge and blood, kidney, heart, thoracic aorta, and superior mesenteric artery were collected for measurement of the protein expression. Results: LPS-induced fall in blood pressure and rise in heart rate were associated with increased MyD88 expression and phosphorylation of TAK1 and I?B-? in cytosolic fractions of the tissues. LPS also caused an increase in both unphosphorylated and phosphorylated NF-?B p65 proteins in the cytosolic and nuclear fractions as well as nuclear translocation of NF-?B p65. In addition, serum miR-150, miR-223, and miR-297 expression levels were increased in LPS-treated rats. These effects of LPS were prevented by 5,14-HEDGE. Conclusions: These results suggest that downregulation of MyD88/TAK1/IKK?/I?B-?/NF-?B pathway as well as decreased circulating miR-150, miR-223, and miR-297 expression levels participate in the protective effect of 5,14-HEDGE against hypotension, tachycardia, and inflammation in the rat model of septic shock.
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