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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2017.1
- 수록면
- 1 - 12 (12page)
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Heme oxygenase-1-derived carbon monoxide prevents inflammatory vascular disorders. To date, there is no clear evidence that HO-1/CO prevents endothelial dysfunction associated with the downregulation of endothelial NO synthesis in human endothelial cells stimulated with TNF-α. Here, we found that the CO-releasing compound CORM-2 prevented TNF-α-mediated decreases in eNOS expression and NO/cGMP production, without affecting eNOS promoter activity, by maintaining the functional activity of the eNOS mRNA 3′-untranslated region. By contrast, CORM-2 inhibited MIR155HG expression and miR-155-5p biogenesis in TNF-α-stimulated endothelial cells, resulting in recovery of the 3′-UTR activity of eNOS mRNA, a target of miR-155-5p. The beneficial effect of CORM-2 was blocked by an NF-κB inhibitor, a miR-155-5p mimic, a HO-1 inhibitor and siRNA against HO-1, indicating that CO rescues TNF-α-induced eNOS downregulation through NF-κB-responsive miR-155-5p expression via HO-1 induction; similar protective effects of ectopic HO-1 expression and bilirubin were observed in endothelial cells treated with TNF-α. Moreover, heme degradation products, except iron and N-acetylcysteine prevented H2O2-mediated miR-155-5p biogenesis and eNOS downregulation. These data demonstrate that CO prevents TNF-α-mediated eNOS downregulation by inhibiting redox-sensitive miR-155-5p biogenesis through a positive forward circuit between CO and HO-1 induction. This circuit may play an important preventive role in inflammatory endothelial dysfunction associated with human vascular diseases.
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참고문헌 (22)
참고문헌 신청
Alderton WK / 2001 / Nitric oxide synthases: structure, function and inhibition / Biochem J 357 : 593 ~ 615
Awolesi MA / 1995 / Cyclic strain upregulates nitric oxide synthase in cultured bovine aortic endothelial cells / J Clin Invest 96 : 1449 ~ 1454
Dulak J / 2008 / Heme oxygenase-1 and carbon monoxide in vascular pathobiology : focus on angiogenesis / Circulation 117 : 231 ~ 241
Fujimoto H / 2004 / Carbon monoxide protects against cardiac ischemia?reperfusion injury in vivo via MAPK and Akt?eNOS pathways / Arterioscler Thromb Vasc Biol 24 : 1848 ~ 1
Hung TH / 2004 / Secretion of tumor necrosis factor-α from human placental tissues induced by hypoxiareoxygenation causes endothelial cell activation in vitro : a potential
Awolesi MA / 1995 / Cyclic strain upregulates nitric oxide synthase in cultured bovine aortic endothelial cells / J Clin Invest 96 : 1449 ~ 1454
Dulak J / 2008 / Heme oxygenase-1 and carbon monoxide in vascular pathobiology : focus on angiogenesis / Circulation 117 : 231 ~ 241
Fujimoto H / 2004 / Carbon monoxide protects against cardiac ischemia?reperfusion injury in vivo via MAPK and Akt?eNOS pathways / Arterioscler Thromb Vasc Biol 24 : 1848 ~ 1
Hung TH / 2004 / Secretion of tumor necrosis factor-α from human placental tissues induced by hypoxiareoxygenation causes endothelial cell activation in vitro : a potential
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