Kalinec Gilda, Thein Pru, Park Channy, Kalinec Federico
Laboratory of Auditory Cell Biology, Department of Head & Neck Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Laboratory of Auditory Cell Biology, Department of Head & Neck Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Hear Res. 2016 May;335:105-117. doi: 10.1016/j.heares.2016.02.019. Epub 2016 Feb 27.
The House Ear Institute-Organ of Corti 1 (HEI-OC1) is one of the few, and arguable the most used, mouse auditory cell line available for research purposes. Originally proposed as an in vitro system for screening of ototoxic drugs, it has been used to investigate, among other topics, apoptotic pathways, autophagy and senescence, mechanism of cell protection, inflammatory responses, cell differentiation, effects of hypoxia, oxidative and endoplasmic reticulum stress, and expression of molecular channels and receptors. However, the use of different techniques with different goals resulted in apparent contradictions on the actual response of these cells to some specific treatments. We have now performed studies to characterize the actual response of HEI-OC1 cells to a battery of commonly used pharmacological drugs. We evaluated cell toxicity, apoptosis, viability, proliferation, senescence and autophagy in response to APAP (acetaminophen), cisplatin, dexamethasone, gentamicin, penicillin, neomycin, streptomycin, and tobramycin, at five different doses and two time-points (24 and 48 h), by flow cytometry techniques and caspase 3/7, MTT, Cytotoxicity, BrdU, Beclin1, LC3 and SA-β-galactosidase assays. We also used HEK-293 and HeLa cells to compare some of the responses of these cells to those of HEI-OC1. Our results indicate that every cell line responds to the each drug in a different way, with HEI-OC1 cells showing a distinctive sensitivity to at least one of the mechanisms under study. Altogether, our results suggest that the HEI-OC1 might be a useful model to investigate biological responses associated with auditory cells, including auditory sensory cells, but a careful approach would be necessary at the time of evaluating drug effects.
耳科研究所-柯蒂氏器1（HEI-OC1）细胞系是少数几种可用于研究目的的小鼠听觉细胞系之一，并且可以说是使用最为广泛的一种。该细胞系最初被提议作为筛选耳毒性药物的体外系统，目前已被用于研究凋亡途径、自噬和衰老、细胞保护机制、炎症反应、细胞分化、缺氧效应、氧化应激和内质网应激以及分子通道和受体的表达等诸多课题。然而，由于使用了不同技术并针对不同目标，导致这些细胞对某些特定处理的实际反应出现了明显矛盾。我们现在开展了研究，以明确HEI-OC1细胞对一系列常用药物的实际反应。我们通过流式细胞术以及半胱天冬酶3/7、MTT、细胞毒性、BrdU、Beclin1、LC3和SA-β-半乳糖苷酶检测，评估了HEI-OC1细胞在五个不同剂量以及两个时间点（24小时和48小时）对乙酰氨基酚、顺铂、地塞米松、庆大霉素、青霉素、新霉素、链霉素和妥布霉素的细胞毒性、凋亡、活力、增殖、衰老和自噬情况。我们还使用了HEK-293和HeLa细胞来比较这些细胞与HEI-OC1细胞的一些反应。我们的结果表明，每种细胞系对每种药物的反应都不同，HEI-OC1细胞对所研究的至少一种机制表现出独特的敏感性。总体而言，我们的结果表明，HEI-OC1细胞可能是研究与听觉细胞（包括听觉感觉细胞）相关的生物学反应的有用模型，但在评估药物效果时需要谨慎对待。
