Lemire J, Mailloux R, Puiseux-Dao S, Appanna V D
Department of Chemistry and Biochemistry, Laurentian University, Sudbury, Ontario, Canada.
J Neurosci Res. 2009 May 1;87(6):1474-83. doi: 10.1002/jnr.21965.
Although aluminum (Al), a known environmental toxin, has been implicated in a variety of neurological disorders, the molecular mechanism responsible for these conditions is not fully understood. In this report, we demonstrate the ability of Al to trigger mitochondrial dysfunction and ineffective adenosine triphosphate (ATP) production. This situation severely affected cytoskeletal dynamics. Whereas the control cells had well-defined structures, the Al-exposed astrocytoma cells appeared as globular structures. Creatine kinase (CK) and profilin-2, two critical modulators of cellular morphology, were markedly diminished in the astrocytoma cells treated with Al. Antioxidants such as alpha-ketoglutarate and N-acetylcysteine mitigated the occurrence of the globular-shaped cells promoted by Al toxicity. Taken together, these data reveal an intricate link between ATP metabolism and astrocytic dysfunction and provide molecular insights into the pathogenesis of Al-induced neurological diseases.
尽管铝（Al）作为一种已知的环境毒素，已被认为与多种神经疾病有关，但其导致这些病症的分子机制尚未完全明确。在本报告中，我们证明了铝引发线粒体功能障碍和三磷酸腺苷（ATP）生成无效的能力。这种情况严重影响了细胞骨架动力学。对照细胞具有明确的结构，而暴露于铝的星形细胞瘤细胞则呈现为球状结构。肌酸激酶（CK）和原肌球蛋白2这两种细胞形态的关键调节因子，在用铝处理的星形细胞瘤细胞中显著减少。诸如α-酮戊二酸和N-乙酰半胱氨酸等抗氧化剂减轻了由铝毒性促进的球状细胞的出现。综上所述，这些数据揭示了ATP代谢与星形细胞功能障碍之间的复杂联系，并为铝诱导的神经疾病的发病机制提供了分子层面的见解。
