Loss of TRPM2 function protects against irradiation-induced salivary gland dysfunction.
Loss of TRPM2 function protects against irradiation-induced salivary gland dysfunction.
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DOI：
10.1038/ncomms2526
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发表时间：
2013
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
--
作者：
由于唾液腺损伤导致的口干症是头颈部癌症放疗的永久性和使人衰弱的副作用。保护或恢复唾液腺功能的有效治疗是不可用的。在这里，我们报告说，辐射治疗导致激活的钙渗透通道，瞬时电位melastin-like 2（TRPM 2），通过刺激的聚ADP-核糖聚合酶。重要的是，照射诱导TRPM 2 +/+小鼠唾液腺液体分泌的不可逆损失，而TRPM 2 −/−小鼠中观察到短暂损失，照射后30天恢复>60%。用自由基清除剂Tempol或PARP 1抑制剂3-氨基苯甲酰胺治疗TRPM 2 +/+小鼠，可减弱辐射诱导的TRPM 2活化，并诱导唾液分泌显著恢复。此外，TPL（4-羟基-2，2，6，6-四甲基哌啶-N-氧基）诱导受辐射TRPM 2 −/−小鼠的功能完全恢复。这些新的数据表明，TRPM 2被辐射激活，通过PARP 1激活，并有助于唾液腺功能的不可逆损失。
Xerostomia as a result of salivary gland damage is a permanent and debilitating side effect of radiotherapy for head and neck cancers. Effective treatments for protecting, or restoring, salivary gland function are not available. Here we report that irradiation treatment leads to activation of the calcium-permeable channel, transient potential melastatin-like 2 (TRPM2), via stimulation of poly-ADP-ribose polymerase. Importantly, irradiation induced an irreversible loss of salivary gland fluid secretion in TRPM2+/+ mice while a transient loss was seen in TRPM2−/− mice with >60% recovery by 30 days after irradiation. Treatment of TRPM2+/+ mice with the free radical scavenger Tempol or the PARP1 inhibitor 3-aminobenzamide attenuated irradiation-induced activation of TRPM2 and induced significant recovery of salivary fluid secretion. Furthermore, TPL (4-hydroxy-2,2,6,6-tetramethylpiperidine- N-oxyl) induced complete recovery of function in irradiated TRPM2−/− mice. These novel data demonstrate that TRPM2 is activated by irradiation, via PARP1 activation, and contributes to irreversible loss of salivary gland function.
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DOI：
10.1016/j.ijrobp.2004.12.051
发表时间：
2005-07-15
影响因子：
7
作者：
Konings, AWT;Coppes, RP;Vissink, A
通讯作者：
Vissink, A
影响因子：
8
作者：
Blenn, C.;Wyrsch, P.;Bader, J.;Bollhalder, M.;Althaus, Felix R.
通讯作者：
Althaus, Felix R.
影响因子：
1.3
作者：
De la Cal, C.;Fernandez-Solari, J.;Elverdin, J. C.
通讯作者：
Elverdin, J. C.
影响因子：
11.5
作者：
Cotrim, AP;Sowers, AL;Baum, BJ
通讯作者：
Baum, BJ
影响因子：
11.5
作者：
Albert, Jeffrey M.;Cao, Carolyn;Lu, Bo
通讯作者：
Lu, Bo