Maulucci Giuseppe, Troiani Diana, Eramo Sara Letizia Maria, Paciello Fabiola, Podda Maria Vittoria, Paludetti Gaetano, Papi Massimiliano, Maiorana Alessandro, Palmieri Valentina, De Spirito Marco, Fetoni Anna Rita
Istituto di Fisica, Università Cattolica (UCSC), Roma, Italy.
Istituto di Fisiologia, Università Cattolica (UCSC), Roma, Italy.
Biochim Biophys Acta. 2014 Jul;1840(7):2192-202. doi: 10.1016/j.bbagen.2014.04.005. Epub 2014 Apr 13.
Noise exposure impairs outer hair cells (OHCs). The common basis for OHC dysfunction and loss by acoustic over-stimulation is represented by reactive oxygen species (ROS) overload that may affect the membrane structural organization through generation of lipid peroxidation.
Here we investigated in OHC different functional zones the mechanisms linking metabolic functional state (NAD(P)H intracellular distribution) to the generation of lipid peroxides and to the physical state of membranes by two photon fluorescence microscopy.
In OHCs of control animals, a more oxidized NAD(P)H redox state is associated to a less fluid plasma membrane structure. Acoustic trauma induces a topologically differentiated NAD(P)H oxidation in OHC rows, which is damped between 1 and 6h. Peroxidation occurs after 4h from noise insult, while ROS are produced in the first 0.2h and damage cells for a period of time after noise exposure has ended (7.5h) when a decrease of fluidity of OHC plasma membrane occurs. OHCs belonging to inner rows, characterized by a lower metabolic activity with respect to other rows, show less severe metabolic impairment.
Our data indicate that plasma membrane fluidity is related to NAD(P)H redox state and lipid peroxidation in hair cells.
Our results could pave the way for therapeutic intervention targeting the onset of redox umbalance.
噪声暴露会损害外毛细胞（OHC）。声学过度刺激导致OHC功能障碍和损失的常见原因是活性氧（ROS）过载，其可能通过产生脂质过氧化作用影响膜结构组织。
在此，我们通过双光子荧光显微镜研究了OHC不同功能区中代谢功能状态（细胞内NAD(P)H分布）与脂质过氧化物生成以及膜物理状态之间的联系机制。
在对照动物的OHC中，NAD(P)H氧化还原状态越高，质膜结构流动性越低。声学创伤在OHC排中诱导拓扑分化的NAD(P)H氧化，在1至6小时之间减弱。噪声损伤约4小时后发生过氧化，而ROS在最初的0.2小时内产生，并在噪声暴露结束后一段时间（约7.5小时）内损伤细胞，此时OHC质膜流动性降低。属于内排的OHC，其代谢活性相对于其他排较低，显示出较轻的代谢损伤。
我们的数据表明，质膜流动性与毛细胞中的NAD(P)H氧化还原状态和脂质过氧化有关。
我们的结果可能为针对氧化还原失衡发生的治疗干预铺平道路。
