Sangchot P, Sharma S, Chetsawang B, Porter J, Govitrapong P, Ebadi M
Department of Pharmacology, Physiology, and Therapeutics, University of North Dakota School of Medicine and Health Sciences, Grand Forks, N.D. 58203, USA.
Dev Neurosci. 2002;24(2-3):143-53. doi: 10.1159/000065700.
One of the defining characteristics of neurodegenerative diseases, including Parkinson's disease, is an abnormal accumulation of iron in the affected brain areas. By using SK-N-SH, a dopaminergic cell line, we have found that iron (100-250 microM FeSO(4)) decreased cell viability, increased lipid peroxidation, and the said effects were blocked by deferoxamine (DFO: 10 microM). Furthermore, DFO, in the absence of iron, enhanced the level of adenosine triphosphate (ATP), but caused chromatin condensation and cell death. Morphological studies revealed that iron (50-100 microM) altered mitochondrial morphology, disrupted nuclear membrane, and translocated alpha-synuclein from perinuclear region into the disrupted nucleus. The results of these studies suggest that DFO is able to block and attenuate iron-mediated oxidative stress. However, in the absence of excess iron, DFO itself may have deleterious effects on the morphology and hence integrity of dopaminergic neurons.
包括帕金森病在内的神经退行性疾病的一个典型特征是，在受影响的脑区中铁异常蓄积。通过使用多巴胺能细胞系SK-N-SH，我们发现铁（100 - 250微摩尔硫酸亚铁）降低了细胞活力，增加了脂质过氧化，而去铁胺（DFO：10微摩尔）可阻断上述作用。此外，在没有铁的情况下，DFO提高了三磷酸腺苷（ATP）水平，但导致了染色质凝聚和细胞死亡。形态学研究表明，铁（50 - 100微摩尔）改变了线粒体形态，破坏了核膜，并使α-突触核蛋白从核周区域转移到破裂的细胞核中。这些研究结果表明，DFO能够阻断并减轻铁介导的氧化应激。然而，在没有过量铁的情况下，DFO本身可能对多巴胺能神经元的形态以及完整性产生有害影响。
