Zinc-induced neuronal death in cortical neurons.
Zinc-induced neuronal death in cortical neurons.
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发表时间：
2000-06
影响因子：
1.6
通讯作者：
D. Lobner;L. Canzoniero;P. Manzerra;F. Gottron;H. Ying;M. Knudson;M. Tian;L. Dugan;G. Kerchner;C. Sheline;S. Korsmeyer;D. Choi
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文献类型：
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作者：
D. Lobner;L. Canzoniero;P. Manzerra;F. Gottron;H. Ying;M. Knudson;M. Tian;L. Dugan;G. Kerchner;C. Sheline;S. Korsmeyer;D. Choi
虽然Zn 2+通常在大脑中储存和释放，但过度暴露于细胞外Zn 2+可能具有神经毒性。本研究的目的是确定的类型的神经元细胞死亡，坏死与凋亡，锌+暴露诱导。在接下来的24小时内，向鼠神经元和神经胶质细胞培养物的浴液中加入10-50 μ M ZnCl 2诱导，Zn 2+浓度依赖性神经元死亡;当Zn 2+浓度高于30 μ M时，也会发生一些神经胶质细胞死亡。20 μ M Zn 2+诱导的神经元死亡的特征是粗染色质凝聚，凋亡小体的形成，和核小体间的DNA片段化。在从bax基因缺失小鼠制备的皮质细胞培养物中，以及通过半胱天冬酶抑制剂苄氧羰基-Val-Ala-Asp-CH 2F（ZVAD，100 μ M），但不通过NMDA受体拮抗剂D-2-氨基-5-膦酰基戊酸酯（D-APV，200 μ M），它被减弱。相比之下，50 μ M Zn 2+诱导的神经元死亡的特征是质膜破坏和随机DNA片段化;这种死亡被D-APV减弱，但对ZVAD或Bax缺失几乎不敏感。这些结果表明，Zn ~（2+）可诱导细胞死亡，其特征为凋亡或坏死，这取决于Zn ~（2+）暴露的强度。
Although Zn2+ is normally stored and released in the brain, excessive exposure to extracellular Zn2+ can be neurotoxic. The purpose of the present study was to determine the type of neuronal cell death, necrosis versus apoptosis, induced by Zn2+ exposure. Addition of 10-50 microM ZnCl2 to the bathing medium of murine neuronal and glial cell cultures induced, over the next 24 hrs., Zn2+-concentration-dependent neuronal death; some glial death also occurred with Zn2+ concentrations above 30 microM. The neuronal death induced by 20 microM Zn2+ was characterized by coarse chromatin condensation, the formation of apoptotic bodies, and internucleosomal DNA fragmentation. It was attenuated in cortical cell cultures prepared from mice null for the bax gene, and by the caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp-CH2F (ZVAD, 100 microM), but not by the NMDA receptor antagonist, D-2-amino-5-phosphonovalerate (D-APV, 200 microM ). In contrast, the neuronal death induced by 50 microM Zn2+ was characterized by plasma membrane disruption and random DNA fragmentation; this death was attenuated by D-APV, but exhibited little sensitivity to ZVAD or deletion of bax. These results suggest that Zn2+ can induce cell death with characteristics of either apoptosis or necrosis, depending on the intensity of the Zn2+ exposure.