Pituitary adenylate cyclase activating polypeptide reduces A-type K+ currents and caspase activity in cultured adult mouse olfactory neurons
Pituitary adenylate cyclase activating polypeptide reduces A-type K+ currents and caspase activity in cultured adult mouse olfactory neurons
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DOI：
10.1016/j.neuroscience.2005.05.007
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发表时间：
2005-01-01
期刊：
影响因子：
3.3
通讯作者：
Lucero, MT
中科院分区：
文献类型：
--
作者：
Han, P;Lucero, MT
垂体腺苷酸环化酶激活多肽已被证明可以减少新生儿小脑和嗅觉受体神经元的凋亡，但其潜在的机制尚未阐明。此外，垂体腺苷酸环化酶激活多肽的神经保护作用尚未在成人组织中进行研究。为了研究垂体腺苷酸环化酶激活多肽对神经元凋亡的影响，我们在体外检测了成人嗅觉受体神经元中caspase的激活。有趣的是，我们发现垂体腺苷酸环化酶激活多肽的保护作用与缺乏4-氨基吡啶（IC50 = 144 μ M）敏感的快速失活钾电流（通常称为a型电流）有关。在40 nM垂体腺苷酸环化酶激活多肽38存在下，a型电流和激活的半胱天冬酶均显著降低。垂体腺苷酸环化酶激活多肽可通过抑制磷脂酶C途径而非腺苷酸环化酶途径阻断a型电流还原。我们观察到5mm4 -氨基吡啶模拟垂体腺苷酸环化酶激活多肽对caspase的抑制作用，表明a型电流参与了细胞凋亡。这项工作有助于我们越来越多地了解钾电流与半胱天冬酶的激活有关，从而影响细胞生死之间的平衡。(c) 2005年由Elsevier Ltd代表IBRO出版。
Pituitary adenylate cyclase activating polypeptide has been shown to reduce apoptosis in neonatal cerebellar and olfactory receptor neurons, however the underlying mechanisms have not been elucidated. In addition, the neuroprotective effects of pituitary adenylate cyclase activating polypeptide have not been examined in adult tissues. To study the effects of pituitary adenylate cyclase activating polypeptide on neurons in apoptosis, we measured caspase activation in adult olfactory receptor neurons in vitro. Interestingly, we found that the protective effects of pituitary adenylate cyclase activating polypeptide were related to the absence of a 4-aminopyridine (IC50 = 144 mu M) sensitive rapidly inactivating potassium current often referred to as A-type current. In the presence of 40 nM pituitary adenylate cyclase activating polypeptide 38, both A-type current and activated caspases were significantly reduced. A-type current reduction by pituitary adenylate cyclase activating polypeptide was blocked by inhibiting the phospholipase C pathway, but not the adenylyl cyclase pathway. Our observation that 5 mM 4-aminopyridine mimicked the caspase inhibiting effects of pituitary adenylate cyclase activating polypeptide indicates that A-type current is involved in apoptosis. This work contributes to our growing understanding that potassium currents are involved with the activation of caspases to affect the balance between cell life and death. (c) 2005 Published by Elsevier Ltd on behalf of IBRO.