RNA-seq of Odora cells exposed to zinc gluconate

Zinc is both an essential and potentially toxic metal. It is widely believed that oral zinc supplementation can reduce the effects of the common cold; however, there is strong clinical evidence that intranasal (IN) zinc gluconate (ZG) gel treatment for this purpose causes anosmia, or the loss of the sense of smell, in humans. Using the rat olfactory neuron cell line, Odora, we investigated the molecular mechanism by which zinc exposure exerts its toxic effects on olfactory neurons. Following treatment of Odora cells with 100 and 200 µM ZG for 0-24 h, RNA-seq and in silico analyses revealed up-regulation of pathways associated with zinc metal response, oxidative stress, and ATP production. We observed that Odora cells recovered from zinc-induced oxidative stress, but ATP depletion persisted with longer exposure to ZG. ZG exposure increased levels of NLRP3 and IL-1ß protein levels in a time-dependent manner, suggesting that zinc exposure may cause an inflammasome-mediated cell death, pyroptosis, in olfactory neurons.锌（Zinc）既是人体必需的金属元素，同时也具有潜在毒性。学界普遍认为口服锌补充剂可缓解普通感冒的症状；然而，大量临床证据表明，以此为目的使用鼻内（intranasal，IN）葡萄糖酸锌（zinc gluconate，ZG）凝胶治疗，会导致人类出现嗅觉丧失（anosmia），即嗅觉功能完全丧失。本研究采用大鼠嗅觉神经元细胞系Odora（Odora），探究锌暴露对嗅觉神经元产生毒性作用的分子机制。将Odora细胞以100和200 μM的ZG分别处理0至24小时后，通过RNA测序（RNA-seq）与计算机模拟分析（in silico）发现，金属锌应答、氧化应激及ATP生成相关通路均出现表达上调。我们观察到，Odora细胞可从锌诱导的氧化应激中恢复，但随着ZG暴露时长增加，ATP耗竭的状态仍持续存在。ZG暴露会以时间依赖性方式升高NLRP3与白细胞介素1β（IL-1β）的蛋白水平，这表明锌暴露可能会诱导嗅觉神经元发生炎性小体介导的细胞死亡——焦亡（pyroptosis）。