Membrane disruption: An early event of hair cell apoptosis induced by exposure to intense noise

Membrane disruption: An early event of hair cell apoptosis induced by exposure to intense noise
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DOI:
10.1016/j.brainres.2008.08.043
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发表时间:
2008-11-06
期刊:
影响因子:
2.9
通讯作者:
Zheng, Gui Liang
Zheng, Gui Liang
中科院分区:
医学3区
文献类型:
--
作者:
Hu, Bo Hua;Zheng, Gui Liang

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在暴露于强噪声后经历凋亡的毛细胞中发现了膜渗漏。然而,目前尚不清楚这种膜损伤是凋亡性变性还是直接机械应力的结果。本研究旨在研究细胞凋亡发生前是否发生膜损伤,并确定膜损伤的水平。龙猫暴露于155 dB峰值SPL的脉冲噪声。噪声引起的膜损伤进行了评估功能,使用膜示踪剂与梯度分子大小(碘化丙啶和FITC-葡聚糖与分子大小为3,40,500,和2000 kDa),形态学,使用二氧染色和半薄切片。这项研究揭示了两个主要发现。首先,暴露于强噪声引起膜渗透性的迅速增加,膜渗漏的发生先于核凝聚的表现。这表明在细胞凋亡中观察到的早期膜损伤是机械应力的直接结果。第二,膜损伤的水平是严重的,允许3 kDa和40 kDa的FITC-葡聚糖进入,但膜没有被完全破坏,如通过保留排除500 kDa和2000 kDa的FITC-葡聚糖分子的能力和维持细胞边界所证明的。值得注意的是,尽管膜损伤,毛细胞继续经历凋亡过程,导致产生一种具有早期膜损伤的凋亡类型。(C)2008 Elsevier B. V.保留所有权利。
Membrane leakage has been found in hair cells undergoing apoptosis following exposure to intense noise. However, it is not known whether this membrane damage is the consequence of apoptotic degeneration or direct mechanical stress. The current study was designed to investigate whether membrane damage occurred before the onset of apoptosis and to determine the level of the membrane damage. Chinchillas were exposed to an impulse noise at 155 dB peak SPL. The noise-induced membrane damage was assessed functionally, using membrane tracers with graded molecular sizes (propidium iodide and FITC-dextrans with molecular sizes of 3, 40, 500, and 2000 kDa), and morphologically, using DiO staining and semithin sections. The study revealed two major findings. First, exposure to intense noise caused a rapid increase in membrane permeability, and the onset of membrane leakage preceded the manifestation of nuclear condensation. This indicates that the early membrane damage observed in apoptosis is the direct consequence of mechanical stress. Second, the level of membrane damage was severe, allowing the entry of 3 kDa and 40 kDa FITC-dextrans, but the membrane was not completely broken down, as evidenced by the preservation of the ability to exclude 500 kDa and 2000 kDa FITC-dextran molecules and the maintenance of the cell boundary. Notably, despite the membrane damage, hair cells continue to undergo the apoptotic process, leading to the generation of a type of apoptosis with early membrane damage. (C) 2008 Elsevier B.V. All rights reserved.