Carr V M, Menco B P, Yankova M P, Morimoto R I, Farbman A I
Department of Neurobiology and Physiology, Northwestern University, Evanston, Illinois 60208-3520, USA.
J Comp Neurol. 2001 Apr 16;432(4):425-39. doi: 10.1002/cne.1112.
Heat shock, or stress, proteins (HSPs) are induced in response to conditions that cause protein denaturation. Activation of cellular stress responses as a protective and survival mechanism is often associated with chemical exposure. One interface between the body and the external environment and chemical or biological agents therein is the olfactory epithelium (OE). To determine whether environmental odorants affect OE HSP expression, rats were exposed to a variety of odorants added to the cage bedding. Odorant exposure led to transient, selective induction of HSP70, HSC70, HSP25, and ubiquitin immunoreactivities (IRs) in supporting cells and subepithelial Bowman's gland acinar cells, two OE non-neuronal cell populations involved with inhalant biotransformation, detoxification, and maintenance of overall OE integrity. Responses exhibited odor specificity and dose dependency. HSP70 and HSC70 IRs occurred throughout the apical region of supporting cells; ubiquitin IR was confined to a supranuclear cone-shaped region. Electron microscopic examination confirmed these observations and, additionally, revealed odor-induced formation of dense vesicular arrays in the cone-like regions. HSP25 IR occurred throughout the entire supporting cell cytoplasm. In contrast to classical stress responses, in which the entire array of stress proteins is induced, no increases in HSP40 and HSP90 IRs were observed. Extended exposure to higher odorant doses caused prolonged activation of the same HSP subset in the non-neuronal cells and severe morphological damage in both supporting cells and olfactory receptor neurons (ORNs), suggesting that non-neuronal cytoprotective stress response mechanisms had been overwhelmed and could no longer adequately maintain OE integrity. Significantly, ORNs showed no stress responses in any of our studies. These findings suggest a novel role for these HSPs in olfaction and, in turn, possible involvement in other normal neurophysiological processes.
热休克蛋白（HSPs），又称应激蛋白，是在导致蛋白质变性的条件下被诱导产生的。细胞应激反应作为一种保护和生存机制的激活通常与化学物质暴露有关。身体与外部环境以及其中的化学或生物制剂之间的一个界面是嗅觉上皮（OE）。为了确定环境气味剂是否会影响OE中HSP的表达，将大鼠暴露于添加到笼垫料中的各种气味剂中。气味剂暴露导致支持细胞和上皮下鲍曼腺腺泡细胞（参与吸入性生物转化、解毒和维持OE整体完整性的两种OE非神经元细胞群体）中HSP70、HSC70、HSP25和泛素免疫反应性（IRs）的短暂、选择性诱导。反应表现出气味特异性和剂量依赖性。HSP70和HSC70 IRs出现在支持细胞的整个顶端区域；泛素IR局限于核上锥形区域。电子显微镜检查证实了这些观察结果，此外，还揭示了气味诱导的锥形区域中致密囊泡阵列的形成。HSP25 IR出现在整个支持细胞胞质中。与经典应激反应中诱导整个应激蛋白阵列不同，未观察到HSP40和HSP90 IRs增加。长时间暴露于更高剂量的气味剂会导致非神经元细胞中相同HSP亚群的长期激活，并对支持细胞和嗅觉受体神经元（ORN）造成严重形态损伤，这表明非神经元细胞保护应激反应机制已不堪重负，无法再充分维持OE的完整性。值得注意的是，在我们所有的研究中，ORN均未表现出应激反应。这些发现表明这些HSPs在嗅觉中具有新的作用，进而可能参与其他正常的神经生理过程。
