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首页> 外文期刊>The Journal of Nutritional Biochemistry >Synergistic induction of ER stress by homocysteine and beta-amyloid in SH-SY5Y cells.
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Synergistic induction of ER stress by homocysteine and beta-amyloid in SH-SY5Y cells.

机译：同型半胱氨酸和β-淀粉样蛋白在SH-SY5Y细胞中协同诱导ER应激。

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Clinical studies have raised the possibility that elevated plasma levels of homocysteine increase the risk of atherosclerosis, stroke and possibly neurodegenerative diseases such as Alzheimer's disease (AD); however, the direct impact of homocysteine on neuron cells and the mechanism by which it could induce neurodegeneration have yet to be clearly demonstrated. Here, we investigated the effect of homocysteine on endoplasmic reticulum (ER) stress, the suggested mechanism of neurotoxicity, in human neuroblastoma SH-SY5Y cells. The effect of homocysteine on amyloid-beta (Abeta)-induced neurotoxicity and the protective activity of folate were also investigated. Homocysteine led to increased expressions of the binding protein (BiP) and the spliced form of X-box-protein (XBP)-1 mRNAs, suggesting activation of the unfolded-protein response and an increase in apoptosis. When cells were cotreated with homocysteine and Abeta, caspase-3 activity was significantly increased, and expressions of BiP and the spliced form of XBP-1 mRNAs were significantly induced. The neurotoxicity of homocysteine was attenuated by the treatment of cells with folate, as determined by caspase-3 activity and apoptotic body staining. These findings indicate that homocysteine induces ER stress and, ultimately, apoptosis and sensitizes neurons to amyloid toxicity via the synergistic induction of ER stress. Furthermore, a neuroprotective effect of folate against homocysteine-induced toxicity was also observed. Therefore, the findings of our study suggest that ER stress-induced homocysteine toxicity may play an important physiological role in enhancing the pathogenesis of Abeta-induced neuronal degeneration.
机译：临床研究增加了血浆同型半胱氨酸水平升高会增加动脉粥样硬化，中风以及可能的神经退行性疾病（如阿尔茨海默氏病（AD））风险的可能性。然而，高半胱氨酸对神经元细胞的直接影响及其诱导神经退行性的机制尚未清楚地证明。在这里，我们调查了高半胱氨酸对人神经母细胞瘤SH-SY5Y细胞内质网（ER）应激（神经毒性的建议机制）的影响。还研究了高半胱氨酸对淀粉样β（Abeta）诱导的神经毒性和叶酸的保护活性的影响。同型半胱氨酸导致结合蛋白（BiP）和X盒蛋白（XBP）-1 mRNA的剪接形式表达增加，表明未折叠蛋白应答的激活和细胞凋亡的增加。当用高半胱氨酸和Abeta共同处理细胞时，caspase-3活性显着增加，并且BiP的表达和XBP-1 mRNA的剪接形式被显着诱导。高半胱氨酸的神经毒性通过用叶酸处理细胞而减弱，这由caspase-3活性和细胞凋亡染色确定。这些发现表明，同型半胱氨酸诱导内质网应激，并最终通过协同诱导内质网应激引起神经元凋亡，并使神经元对淀粉样蛋白毒性敏感。此外，还观察到叶酸对高半胱氨酸诱导的毒性的神经保护作用。因此，我们的研究结果表明，内质网应激引起的同型半胱氨酸毒性可能在增强Abeta引起的神经元变性的发病机理中起重要的生理作用。

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