Hyperoxia increases the elastic modulus of alveolar epithelial cells through Rho kinase.
Hyperoxia increases the elastic modulus of alveolar epithelial cells through Rho kinase.
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DOI：
10.1111/febs.12661
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发表时间：
2014-02
期刊：
影响因子：
--
通讯作者：
Waters CM
中科院分区：
文献类型：
--
作者：
Wilhelm KR;Roan E;Ghosh MC;Parthasarathi K;Waters CM
急性肺损伤的患者在机械呼吸过程中被给予高浓度的氧气，虽然高氧和机械通风都是必要的，但每一种都可能独立地导致额外的损伤。然而，导致损伤的确切机制还不是很清楚。我们推测，肺泡上皮细胞可能更容易受到机械通气造成的损伤，因为高氧通过GTPase RhoA及其效应蛋白Rho Kinase(ROCK)增加了f-肌动蛋白的形成，导致细胞变得更加僵硬。我们观察了培养的小鼠肺泡上皮细胞(MLE-12)在常氧和高氧(48h)条件下的细胞骨架结构。我们还在压痕模式下使用原子力显微镜(AFM)测量了细胞弹性(E)。高氧导致f-肌动蛋白应激纤维和纤维束形成增加，g-肌动蛋白和f-肌动蛋白增加，核面积增大，核高度降低，细胞变硬(E值较高)。Rho激酶抑制剂(ROCK)Y-27632可显著降低E，阻止细胞骨架改变，但对核的高度和面积无明显影响。当细胞随后被循环拉伸时，预先暴露在高氧中会促进细胞脱离，但岩石抑制剂阻止了这一效应。高氧导致纽蛋白斑块增厚，岩石抑制减少明显的斑块粘连形成。高氧和Y-27632处理均显著降低粘着斑激酶的磷酸化水平。在拉伸过程中，高氧会增加细胞的硬度，促进细胞的脱落。通过对岩石的抑制，这些效果得到改善。
Patients with acute lung injury are administered high concentrations of oxygen during mechanical ventilation, and while both hyperoxia and mechanical ventilation are necessary, each can independently cause additional injury. However, the precise mechanisms that lead to injury are not well understood. We hypothesized that alveolar epithelial cells may be more susceptible to injury caused by mechanical ventilation because hyperoxia causes cells to be stiffer due to increased f-actin formation via the GTPase RhoA and its effecter Rho kinase (ROCK). We examined cytoskeletal structures in cultured murine lung alveolar epithelial cells (MLE-12) under normoxic and hyperoxic (48h) conditions. We also measured cell elasticity (E) using atomic force microscopy (AFM) in the indenter mode. Hyperoxia caused increased f-actin stress fibers and bundle formation, an increase in g- and f-actin, an increase in nuclear area and a decrease in nuclear height, and cells became stiffer (higher E). Treatment with an inhibitor (Y-27632) of Rho kinase (ROCK) significantly decreased E and prevented the cytoskeletal changes, while it did not influence the nuclear height and area. Pre-exposure of cells to hyperoxia promoted detachment when cells were subsequently stretched cyclically, but the ROCK inhibitor prevented this effect. Hyperoxia caused thickening of vinculin focal adhesion plaques, and inhibition of ROCK reduced the formation of distinct focal adhesion plaques. Phosphorylation of focal adhesion kinase was significantly reduced by both hyperoxia and treatment with Y-27632. Hyperoxia caused increased cell stiffness and promoted cell detachment during stretch. These effects were ameliorated by inhibition of ROCK.
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影响因子：
3.6
作者：
Foster, Cherie D.;Varghese, Linda S.;Guttentag, Susan H.
通讯作者：
Guttentag, Susan H.
DOI：
10.1152/ajplung.00292.2011
发表时间：
2012-05-01
影响因子：
4.9
作者：
Birukova, Anna A.;Tian, Yufeng;Birukov, Konstantin G.
通讯作者：
Birukov, Konstantin G.
影响因子：
5.5
作者：
DiPaolo, Brian C.;Lenormand, Guillaume;Margulies, Susan S.
通讯作者：
Margulies, Susan S.
DOI：
10.1152/ajplung.00022.2004
发表时间：
2004-12-01
影响因子：
4.9
作者：
Desai, LP;Aryal, AM;Waters, CM
通讯作者：
Waters, CM
DOI：
10.1016/s0006-291x(03)01165-3
发表时间：
2003-07-25
影响因子：
3.1
作者：
Chen, CS;Alonso, JL;Ingber, DE
通讯作者：
Ingber, DE