3-benzyl-5-((2-nitrophenoxy)methyl)dihydrofuran-2(3h)-one and Acute-Lung-Injury

3-benzyl-5-((2-nitrophenoxy)methyl)dihydrofuran-2(3h)-one has been researched along with Acute-Lung-Injury* in 1 studies

Other Studies

1 other study(ies) available for 3-benzyl-5-((2-nitrophenoxy)methyl)dihydrofuran-2(3h)-one and Acute-Lung-Injury

Article	Year
The SIRT1 inhibitor EX-527 suppresses mTOR activation and alleviates acute lung injury in mice with endotoxiemia. Innate immunity, 2017, Volume: 23, Issue:8 It is generally regarded that Sirtuin 1 (SIRT1), a longevity factor in mammals, acts as a negative regulator of inflammation. However, recent studies also found that SIRT1 might be a detrimental factor under certain inflammatory circumstance. In this study, the potential pathophysiological roles and the underlying mechanisms of SIRT1 in a mouse model with endotoxemia-associated acute lung injury were investigated. The results indicated that treatment with the selective SIRT1 inhibitor EX-527 suppressed LPS-induced elevation of TNF-α and IL-6 in plasma. Treatment with EX-527 attenuated LPS-induced histological abnormalities in lung tissue, which was accompanied with decreased myeloperoxidase level and suppressed induction of tissue factor and plasminogen activator inhibitor-1. Treatment with EX-527 also suppressed LPS-induced phosphorylation of eukaryotic translation initiation factor-binding protein 1 (4E-BP1). Co-administration of a mammalian target of rapamycin (mTOR) activator 3-benzyl-5-[(2-nitrophenoxy) methyl]-dihydrofuran-2 (3H)-one (3BDO) abolished the inhibitory effects of EX-527 on 4E-BP1 phosphorylation. Meanwhile, the inhibitory effects of EX-527 on IL-6 induction and the beneficial effects of EX-527 on lung injury were partially reversed by 3BDO. This study suggests that selective inhibition of SIRT1 by EX-527 might alleviate endotoxemia-associated acute lung injury partially via suppression of mTOR, which implies that SIRT1 selective inhibitors might have potential value for the pharmacological intervention of inflammatory lung injury. Topics: 4-Butyrolactone; Acute Lung Injury; Adaptor Proteins, Signal Transducing; Animals; Carbazoles; Carrier Proteins; Cell Cycle Proteins; Endotoxemia; Eukaryotic Initiation Factors; Interleukin-6; Lipopolysaccharides; Lung; Male; Mice; Mice, Inbred BALB C; Phosphoproteins; Phosphorylation; Plasminogen Activator Inhibitor 1; Sirtuin 1; Thromboplastin; TOR Serine-Threonine Kinases; Tumor Necrosis Factor-alpha	2017

Article

Year

The SIRT1 inhibitor EX-527 suppresses mTOR activation and alleviates acute lung injury in mice with endotoxiemia.

Innate immunity, 2017, Volume: 23, Issue:8

It is generally regarded that Sirtuin 1 (SIRT1), a longevity factor in mammals, acts as a negative regulator of inflammation. However, recent studies also found that SIRT1 might be a detrimental factor under certain inflammatory circumstance. In this study, the potential pathophysiological roles and the underlying mechanisms of SIRT1 in a mouse model with endotoxemia-associated acute lung injury were investigated. The results indicated that treatment with the selective SIRT1 inhibitor EX-527 suppressed LPS-induced elevation of TNF-α and IL-6 in plasma. Treatment with EX-527 attenuated LPS-induced histological abnormalities in lung tissue, which was accompanied with decreased myeloperoxidase level and suppressed induction of tissue factor and plasminogen activator inhibitor-1. Treatment with EX-527 also suppressed LPS-induced phosphorylation of eukaryotic translation initiation factor-binding protein 1 (4E-BP1). Co-administration of a mammalian target of rapamycin (mTOR) activator 3-benzyl-5-[(2-nitrophenoxy) methyl]-dihydrofuran-2 (3H)-one (3BDO) abolished the inhibitory effects of EX-527 on 4E-BP1 phosphorylation. Meanwhile, the inhibitory effects of EX-527 on IL-6 induction and the beneficial effects of EX-527 on lung injury were partially reversed by 3BDO. This study suggests that selective inhibition of SIRT1 by EX-527 might alleviate endotoxemia-associated acute lung injury partially via suppression of mTOR, which implies that SIRT1 selective inhibitors might have potential value for the pharmacological intervention of inflammatory lung injury.

Topics: 4-Butyrolactone; Acute Lung Injury; Adaptor Proteins, Signal Transducing; Animals; Carbazoles; Carrier Proteins; Cell Cycle Proteins; Endotoxemia; Eukaryotic Initiation Factors; Interleukin-6; Lipopolysaccharides; Lung; Male; Mice; Mice, Inbred BALB C; Phosphoproteins; Phosphorylation; Plasminogen Activator Inhibitor 1; Sirtuin 1; Thromboplastin; TOR Serine-Threonine Kinases; Tumor Necrosis Factor-alpha

2017