Department of Otolaryngology-Head and Neck Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China.
Department of Otolaryngology, Auditory Medical Center, Cheng Hsin General Hospital, Taipei, Taiwan, Republic of China.
Sci Rep. 2018 Jan 9;8(1):125. doi: 10.1038/s41598-017-18536-y.
Cholesteatoma has attracted many studies seeking to uncover its nature and the pathogenesis of related diseases. However, no researchers have explored the mitochondrial bioenergetics of cholesteatoma. The aim of this study was to investigate the energy demand and differential mitochondrial respiration profiles between keratinocytes in external auditory canal (EAC) skin and cholesteatoma samples cultured in normoxic (20% O) and hypoxic (5% O) conditions. Enhanced cellular proliferation of both types of keratinocytes was found in hypoxia compared to normoxia. In 20% O conditions, cholesteatoma keratinocytes exhibited less mitochondrial mass, lower ATP levels, and significantly lower basal oxygen consumption rate (OCR) and reserve capacity compared to normal skin keratinocytes. In contrast, in hypoxic conditions, cholesteatoma keratinocytes showed markedly higher levels in maximal OCR and reserve capacity, as well as lower proton leak OCRs, compared to normal skin keratinocytes. Hypoxia induced the reverse mitochondrial bioenergy profile from that in normoxia between these two types of keratinocytes, implying that an adaptive change of mitochondrial respiration to oxygen fluctuations may develop in cases of cholesteatoma. Such adaptation in response to hypoxic conditions may play a role in explaining the pathogenesis of acquired cholesteatoma.
胆脂瘤吸引了许多研究旨在揭示其性质和相关疾病的发病机制。然而，目前还没有研究人员探索胆脂瘤的线粒体生物能量学。本研究旨在研究在常氧（20% O）和缺氧（5% O）条件下培养的外耳道（EAC）皮肤角质形成细胞和胆脂瘤样本的能量需求和差异线粒体呼吸特征。与常氧相比，缺氧条件下两种类型的角质形成细胞的细胞增殖能力增强。在 20% O 条件下，与正常皮肤角质形成细胞相比，胆脂瘤角质形成细胞的线粒体质量较低，ATP 水平较低，基础耗氧率（OCR）和储备能力显著较低。相比之下，在缺氧条件下，与正常皮肤角质形成细胞相比，胆脂瘤角质形成细胞的最大 OCR 和储备能力明显较高，质子漏 OCR 较低。缺氧在这两种角质形成细胞之间诱导了与常氧相反的线粒体生物能量谱，这表明在胆脂瘤的情况下，线粒体呼吸对氧气波动的适应性变化可能会发生。这种对缺氧条件的适应可能在解释获得性胆脂瘤的发病机制方面发挥作用。
