PACAP protects against TNFα-induced cell death in olfactory epithelium and olfactory placodal cell lines.
PACAP protects against TNFα-induced cell death in olfactory epithelium and olfactory placodal cell lines.
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DOI：
10.1016/j.mcn.2010.07.007
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发表时间：
2010-12
影响因子：
3.5
通讯作者：
Lucero, Mary T.
中科院分区：
文献类型：
--
作者：
Kanekar, Shami;Gandham, Mahendra;Lucero, Mary T.
关键词：
在小鼠嗅上皮（OE），垂体腺苷酸环化酶激活肽（PACAP）保护对轴突切断诱导的细胞凋亡。我们使用小鼠OE来确定PACAP是否在暴露于炎性细胞因子TNFα的过程中保护神经元。用40 ng/ml TNFα ± 40 nM PACAP处理新生小鼠OE的活切片6小时，并用0.5%碘化丙啶对垂死细胞进行活标记。TNFα显著增加死亡细胞的百分比，而与PACAP共孵育可防止细胞死亡。PACAP还阻止了嗅基板（OP）细胞系OP 6和OP 27中TNFα介导的细胞死亡。尽管OP细胞系表达所有三种PACAP受体（PAC 1、VPAC 1、VPAC 2），但PACAP对这些细胞的TNFα保护作用可被特异性PAC 1受体激动剂maxadilan模拟，并被PAC 1拮抗剂PACAP 6 -38消除。用PLC和AC/MAPKK通路的阻断剂或激活剂处理OP细胞系，发现PACAP介导的TNFα保护作用涉及两种通路。因此，PACAP可能通过PAC 1受体发挥作用，以保护神经元免受体内炎性细胞因子释放过程中的细胞死亡，如病毒感染或过敏性鼻炎相关损伤时发生的细胞死亡。
In mouse olfactory epithelium (OE), pituitary adenylate cyclase activating peptide (PACAP) protects against axotomy-induced apoptosis. We used mouse OE to determine whether PACAP protects neurons during exposure to the inflammatory cytokine TNFα. Live slices of neonatal mouse OE were treated with 40 ng/ml TNFα ± 40 nM PACAP for 6 hours and dying cells were live-labeled with 0.5% propidium iodide. TNFα significantly increased the percentage of dying cells while co-incubation with PACAP prevented cell death. PACAP also prevented TNFα-mediated cell death in the olfactory placodal (OP) cell lines, OP6 and OP27. Although OP cell lines express all three PACAP receptors (PAC1, VPAC1,VPAC2), PACAP’s protection of these cells from TNFα was mimicked by the specific PAC1 receptor agonist maxadilan and abolished by the PAC1 antagonist PACAP6–38. Treatment of OP cell lines with blockers or activators of the PLC and AC/MAPKK pathways revealed that PACAP-mediated protection from TNFα involved both pathways. PACAP may therefore function through PAC1 receptors to protect neurons from cell death during inflammatory cytokine release in vivo as would occur upon viral infection or allergic rhinitis-associated injury.
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影响因子：
4.8
作者：
Moro, O;Wakita, K;Tajima, M
通讯作者：
Tajima, M
影响因子：
5.3
作者：
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通讯作者：
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影响因子：
3
作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
3.3
作者：
Han, P;Lucero, MT
通讯作者：
Lucero, MT