Purinergic receptor antagonists inhibit odorant-induced heat shock protein 25 induction in mouse olfactory epithelium
Purinergic receptor antagonists inhibit odorant-induced heat shock protein 25 induction in mouse olfactory epithelium
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DOI：
10.1002/glia.20258
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发表时间：
2006-01-15
期刊：
影响因子：
6.2
通讯作者：
Lucero, MT
中科院分区：
文献类型：
--
作者：
Hegg, CC;Lucero, MT
热休克蛋白(HSP)在暴露于各种生理和环境因素的细胞中积累，如热休克、氧化应激、毒物和气味。缺血、应激和受损的细胞会大量释放三磷酸腺苷。我们的假设是，伤害性刺激(在这种情况下，强烈的气味)会引起嗅觉上皮(OE)中ATP的释放。细胞外ATP是细胞应激信号，通过嘌呤能受体诱导热休克蛋白的表达。在本研究中，体内气味暴露(庚醛或R-香芹酮)导致瑞士Webster小鼠OE中神经胶质样支持细胞中HSP25的选择性诱导，正如先前在大鼠中所显示的那样(Carr等人，2001年)。此外，在体外和体内给予嘌呤能受体拮抗剂苏拉明和pyridoxalphosphate-6-azophenyl-2‘，4’-disulfonic酸(PPADS)可阻断支持细胞中HSP25的表达。急性损伤细胞释放的ATP可以作为细胞和组织损伤的早期信号，引起HSP的表达，并启动应激信号级联反应，以防止进一步的损伤。支持细胞具有很高的解毒能力，从而保护嗅觉上皮免受空气污染物的影响。因此，在支持细胞中强健、快速地诱导热休克蛋白可能有助于在暴露于毒物期间保持OE的完整性。(C)2005年Wiley-Liss，Inc.
Heat shock proteins (HSPs) accumulate in cells exposed to a variety of physiological and environmental factors, such as heat shock, oxidative stress, toxicants, and odorants. Ischemic, stressed, and injured cells release ATP in large amounts. Our hypothesis is that noxious stimulation (in this case, strong odorant) evokes the release of ATP in the olfactory epithelium (OE). Extracellular ATP, a signal of cellular stress, induces the expression of HSPs via purinergic receptors. In the present study, in vivo odorant exposure (heptanal or R-carvone) led to a selective induction of HSP25 in glia-like sustentacular cells in the Swiss Webster mouse OE, as previously shown in rats (Carr et al., 2001). Furthermore, in vitro and in vivo administration of purinergic receptor antagonists suramin and pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS) blocked the expression of HSP25 immunoreactivity in sustentacular cells. ATP released by acutely injured cells could act as an early signal of cell and tissue damage, causing HSP expression and initiating a stress signaling cascade to protect against further damage. Sustentacular cells have a high capacity to detoxify xenobiotics and thereby protect the olfactory epithelium from airborne pollutants. Thus, the robust, rapid induction of HSPs in sustentacular cells may help maintain the integrity of the OE during exposure to toxicants. (c) 2005 Wiley-Liss, Inc.