Functional and cytoskeletal changes induced by sublethal injury in proximal tubular epithelial cells.
Functional and cytoskeletal changes induced by sublethal injury in proximal tubular epithelial cells.
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近端肾小管上皮细胞亚致死损伤引起的功能和细胞骨架变化。
DOI：
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发表时间：
1994
影响因子：
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通讯作者：
W. Lieberthal
中科院分区：
文献类型：
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作者：
V. M. Kroshian;A. M. Sheridan;W. Lieberthal
通过在不存在葡萄糖的情况下将培养物中的小鼠近端肾小管（MPT）细胞与氰化物孵育1小时，使其经受ATP消耗。这种损伤导致肌动蛋白细胞骨架的显著改变。这些变化与细胞活力降低无关，因此反映了亚致死性损伤。亚致死性损伤的功能完整性的细胞间紧密连接（TJ）的影响，然后在MPT细胞单层生长在可渗透的支持。在化学缺氧期间，单层细胞对细胞旁标志物甘露醇的渗透性在1小时后逐渐增加至基线的297 +/- 62%。当MPT细胞作为融合单层或单细胞进行研究时，化学缺氧也引起细胞-基质粘附的可逆损失。因此，在非致死性损伤的细胞中，肌动蛋白细胞骨架的破坏导致肾上皮功能的重要可逆性改变，其特征在于TJ的“门”功能受损以及细胞-基质粘附受损。我们推测，不伴有坏死的亚致死性上皮细胞损伤可能导致缺血性肾损伤的肾功能下降。
Mouse proximal tubular (MPT) cells in culture were subjected to ATP depletion by incubating them with cyanide in the absence of dextrose for 1 h. This insult resulted in marked alterations in the actin cytoskeleton. These changes were not associated with a decrease in cell viability and thus reflected sublethal injury. The effect of sublethal injury on the functional integrity of the intercellular tight junction (TJ) was then examined in MPT cell monolayers grown on permeable supports. During chemical anoxia, monolayer permeability to the paracellular marker mannitol progressively increased to 297 +/- 62% of baseline after 1 h. Chemical anoxia also caused a reversible loss in cell-substrate adhesion when MPT cells were studied as confluent monolayers or as single cells. Thus disruption of the actin cytoskeleton in nonlethally injured cells results in important reversible alterations in renal epithelial function characterized by impairment of the "gate" function of the TJ as well as impaired cell-substrate adhesion. We hypothesize that sublethal epithelial cell injury without accompanying necrosis may contribute to the decrement in renal function characteristic of ischemic renal injury.