Sphingolipids in Ventilator Induced Lung Injury: Role of Sphingosine-1-Phosphate Lyase.
Sphingolipids in Ventilator Induced Lung Injury: Role of Sphingosine-1-Phosphate Lyase.
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DOI：
10.3390/ijms19010114
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发表时间：
2018-01-01
影响因子：
5.6
通讯作者：
Natarajan V
中科院分区：
文献类型：
--
作者：
Suryadevara V;Fu P;Ebenezer DL;Berdyshev E;Bronova IA;Huang LS;Harijith A;Natarajan V
在呼吸衰竭患者中进行机械通气（MV）以维持肺功能会导致呼吸机诱导的肺损伤（VILI）。本研究探讨鞘脂和鞘脂代谢酶在VILI中的作用，使用VILI和肺泡上皮细胞的啮齿动物模型进行循环拉伸（CS）。MV（0 PEEP，30 mL/kg，4 h）可增强小鼠肺组织中鞘氨醇-1-磷酸裂解酶（S1 PL）的表达和神经酰胺水平，降低S1 P水平，从而导致肺炎症、损伤和细胞凋亡。S1 P在细胞中的积累是由鞘氨醇激酶（SphK）1和2催化的其合成与由S1 P磷酸酶和S1 PL介导的催化之间的平衡。因此，使用Sgpl 1 +/-和Sphk 1-/-小鼠研究了S1 PL和SphK 1在VILI中的作用。部分基因缺失Sgpl 1保护小鼠免受VILI，而SphK 1的缺失加重了小鼠的VILI。肺泡上皮MLE-12细胞进行病理生理18%的周期性拉伸（CS）表现出增加S1 PL蛋白的表达和神经鞘氨醇碱水平失调相比，生理5%的CS。用S1 PL抑制剂4-脱氧吡哆醇预处理MLE-12细胞，减弱18%CS诱导的屏障功能障碍，最小化细胞凋亡和细胞因子分泌。这些结果表明，增加S1 P水平的S1 PL的抑制可以提供针对VILI的保护。
Mechanical ventilation (MV) performed in respiratory failure patients to maintain lung function leads to ventilator-induced lung injury (VILI). This study investigates the role of sphingolipids and sphingolipid metabolizing enzymes in VILI using a rodent model of VILI and alveolar epithelial cells subjected to cyclic stretch (CS). MV (0 PEEP (Positive End Expiratory Pressure), 30 mL/kg, 4 h) in mice enhanced sphingosine-1-phosphate lyase (S1PL) expression, and ceramide levels, and decreased S1P levels in lung tissue, thereby leading to lung inflammation, injury and apoptosis. Accumulation of S1P in cells is a balance between its synthesis catalyzed by sphingosine kinase (SphK) 1 and 2 and catabolism mediated by S1P phosphatases and S1PL. Thus, the role of S1PL and SphK1 in VILI was investigated using Sgpl1+/− and Sphk1−/− mice. Partial genetic deletion of Sgpl1 protected mice against VILI, whereas deletion of SphK1 accentuated VILI in mice. Alveolar epithelial MLE-12 cells subjected to pathophysiological 18% cyclic stretch (CS) exhibited increased S1PL protein expression and dysregulation of sphingoid bases levels as compared to physiological 5% CS. Pre-treatment of MLE-12 cells with S1PL inhibitor, 4-deoxypyridoxine, attenuated 18% CS-induced barrier dysfunction, minimized cell apoptosis and cytokine secretion. These results suggest that inhibition of S1PL that increases S1P levels may offer protection against VILI.
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影响因子：
9.3
作者：
Fan E;Villar J;Slutsky AS
通讯作者：
Slutsky AS
影响因子：
4.8
作者：
Huang, Long Shuang;Berdyshev, Evgeny;Natarajan, Viswanathan
通讯作者：
Natarajan, Viswanathan
影响因子：
--
作者：
Huang LS;Natarajan V
通讯作者：
Natarajan V
影响因子：
4.8
作者：
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通讯作者：
Proia, RL
DOI：
10.1165/rcmb.2012-0252oc
发表时间：
2013-07-01
影响因子：
6.4
作者：
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通讯作者：
Margulies, Susan S.