Neurotoxin-induced DNA damage is persistent in SH-SY5Y cells and LC neurons.
Neurotoxin-induced DNA damage is persistent in SH-SY5Y cells and LC neurons.
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DOI：
10.1007/s12640-015-9521-4
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发表时间：
2015-05
影响因子：
3.7
通讯作者：
Zhu, Meng-Yang
中科院分区：
文献类型：
--
作者：
Wang, Yan;Musich, Phillip R.;Cui, Kui;Zou, Yue;Zhu, Meng-Yang
神经退行性疾病患者的大脑中有去甲肾上腺素能神经元变性的报道。然而，它们在神经退变过程中的病理特征和潜在的机制仍有待阐明。在本研究中，我们使用神经毒素喜树碱(CPT)诱导神经母细胞瘤SH-SY5Y细胞、正常成纤维细胞以及原代培养的LC和中缝神经元的DNA损伤反应，以检测神经毒素暴露后的细胞反应和修复能力。据我们所知，与成纤维细胞相比，本研究首次表明去甲肾上腺素能SH-SY5Y细胞对CPT引起的DNA损伤和DNA修复缺陷更为敏感。此外，与SH-SY5Y细胞相似，原代培养的LC神经元对CPT引起的DNA损伤更敏感，并且在修复这种损伤方面表现出不足。此外，虽然N-(2-氯乙基)-N-乙基-2-溴苯甲胺(DSP4)暴露也可导致培养的LC神经元DNA损伤，但CPT和DSP4均不能引起中缝核神经元培养的DNA损伤。综上所述，去甲肾上腺素能SH-SY5Y细胞和LC神经元对CPT诱导的DNA损伤非常敏感，并表现出修复缺陷，为体内面对内源性和环境DNA损伤时LC变性的病理特征提供了机制解释。
Degeneration of the noradrenergic neurons has been reported in the brain of patients suffering from neurodegenerative diseases. However, their pathologic characteristics during the neurodegenerative course and underlying mechanisms remain to be elucidated. In the present study, we used the neurotoxincamptothecin (CPT)to induce the DNA damage response in neuroblastoma SH-SY5Y cells, normal fibroblast cells, and primarily cultured LC and raphe neurons to examine cellular responses and repair capabilities after neurotoxin exposure. To our knowledge, the present study is the first to show that noradrenergic SH-SY5Y cells are more sensitive to CPT-induced DNA damage and deficientin DNA repair, as compared to fibroblast cells. Furthermore, similar to SH-SY5Y cells, primarily cultured LC neurons are more sensitive to CPT-induced DNA damage and show a deficiency in repairing this damage. Moreover, while N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4) exposure also results in DNA damage in cultured LC neurons, neither CPT nor DSP4 induce DNA damage in neuronal cultures from the raphe nuclei. Taken together, noradrenergic SH-SY5Y cells and LC neurons are sensitive to CPT-induced DNA damage and exhibit a repair deficiency, providing a mechanistic explanation for the pathologic characteristics of LC degeneration when facing endogenous and environmental DNA-damaging insultsin vivo.
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影响因子：
4.2
作者：
Grudzien, Aneta;Shaw, Pamela;Mesulam, M. Marsel
通讯作者：
Mesulam, M. Marsel
影响因子：
64.8
作者：
Downs, JA;Lowndes, NF;Jackson, SP
通讯作者：
Jackson, SP
老年痴呆症中肾上腺素能投射到大脑皮层（脑室核）的起源神经元的缺失
影响因子：
9.9
作者：
BONDAREFF, W;MOUNTJOY, CQ;ROTH, M
通讯作者：
ROTH, M
影响因子：
12.7
作者：
ARIMA, K;AKASHI, T
通讯作者：
AKASHI, T
影响因子：
5
作者：
DOOLEY, DJ;HEAL, DJ;GOODWIN, GM
通讯作者：
GOODWIN, GM