Oxygen-induced changes in protein synthesis and cell proliferation in cultured lung slices.

Oxygen-induced changes in protein synthesis and cell proliferation in cultured lung slices.
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氧诱导培养肺切片中蛋白质合成和细胞增殖的变化。

DOI:
10.1152/ajplung.1994.267.6.l720
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发表时间:
1994
期刊:
The American journal of physiology
影响因子:
--
通讯作者:
Evans,JN
Evans,JN
中科院分区:
--
文献类型:
--
作者:
Shapiro,PS;Casty,FE;Stirewalt,WS;Leslie,KO;Absher,MP;Evans,JN

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吸入的O2分数升高诱导肺的气道和脉管系统的显著重塑。本研究旨在确定改变O2水平对体外培养肺组织蛋白质合成和细胞增殖的直接影响。用低熔点琼脂糖使大鼠肺膨胀,横切成1 mm的切片,并在10、21、40或70%O2存在下在无血清培养基中培养长达7天。通过光学显微镜和电子显微镜评估,组织结构完整性得以维持。从培养的肺匀浆可溶性蛋白的分数合成率(FSR,%蛋白/天)表现出O2浓度依赖性反应。在70%O2的存在下培养的组织表现出最高的FSR。在21或40%O2中培养的组织的FSR没有差异,并且证明FSR值大于在10%O2中培养的组织。在5-溴-2 '-脱氧尿苷存在下培养的肺切片的实质气体交换区域中对细胞增殖进行组织学评估。21%、40%或70%培养的组织的标记指数表明培养3天后细胞增殖的O2依赖性增加,7天后恢复到基线水平。在10%O2存在下培养的组织显示细胞增殖随时间没有变化。这些数据表明O2对肺细胞生长和增殖有直接影响。此外,这些研究表明,这种体外模型可能适合于进一步了解肺损伤过程中增殖事件的机制基础。
Elevated fractions of inspired O2 induce significant remodeling of the airways and vasculature of the lung. The present study was undertaken to determine the direct effects of altered levels of O2 on protein synthesis and cell proliferation in lung tissue cultured in vitro. Rat lungs were inflated with low-melt agarose, cut transversely into 1-mm sections, and cultured in a serum-free medium for up to 7 days in the presence of 10, 21, 40, or 70% O2. Tissue structure integrity was maintained as assessed by light and electron microscopy. Fractional synthesis rates (FSR, %protein/day) of soluble protein from cultured lung homogenates demonstrated an O2 concentration-dependent response. Tissue cultured in the presence of 70% O2 exhibited the highest FSR. The FSR of tissue cultured in 21 or 40% O2 did not differ and demonstrated FSR values greater than tissue cultured in 10% O2. Cell proliferation was assessed histologically in parenchymal gas-exchange regions of lung slices cultured in the presence of 5-bromo-2'-deoxyuridine. Labeling indexes for tissue cultured in 21, 40, or 70% indicated an O2-dependent increase in cell proliferation after 3 days in culture followed by a return to baseline levels after 7 days. Tissue cultured in the presence of 10% O2 showed no change in cell proliferation over time. The data indicate a direct influence of O2 on lung cell growth and proliferation. Additionally, these studies show that this in vitro model may be suitable for further understanding of the mechanistic basis involved in proliferative events during lung injury.
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