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胍丁胺对鱼藤酮诱导的人 SH-SY5Y 神经母细胞瘤细胞损伤的保护作用:帕金森病模型中的傅里叶变换红外光谱分析。

Protective effects of agmatine in rotenone-induced damage of human SH-SY5Y neuroblastoma cells: fourier transform infrared spectroscopy analysis in a model of Parkinson's disease.

机构信息

Department of Biochemical, Physiological and Nutritional Sciences, Policlinico Universitario G. Martino, Via C. Valeria, 98125, Messina, Italy.

出版信息

Amino Acids. 2012 Feb;42(2-3):775-81. doi: 10.1007/s00726-011-0994-z. Epub 2011 Jul 31.

Abstract

Agmatine is a novel neuromodulator that plays a protective role in the CNS in several models of cellular damage. However, the mechanisms involved in these protective effects in neurodegenerative diseases are poorly understood. Fourier transform infrared (FTIR) spectroscopy analysis detects biomolecular changes in disordered cells and tissues. In this report, we utilize FTIR spectroscopy to characterize the changes in rotenone-induced damage in neuronal-like differentiated SH-SY5Y neuroblastoma cells in the presence or absence of agmatine. The analysis of the FTIR spectra demonstrates significant alterations in rotenone-treated cells, whereas the FTIR spectra obtained after pre-incubation with agmatine (250 nM) significantly reduces these redox alterations and more closely resembles those of the control cells. In particular, rotenone-damaged cells demonstrate spectral alterations related to amide I, which correspond to an increase in β-sheet components, and decreases in the amide II absorption intensity, suggesting a loss of N-H bending and C-N stretching. These alterations were also evident by Fourier self-deconvolution analysis. Thus, rotenone-induced increases in the levels of stretching vibration band related to the protein carboxyl group would account for a significant amount of misfolded proteins in the cell. Agmatine effectively reduces these effects of rotenone on protein structure. In conclusion, antioxidant and scavenging properties of agmatine reduce rotenone-produced cellular damage at the level of protein structure. These, together with other previous observations, demonstrate the therapeutic potential of agmatine in the treatment of Parkinson's disease.

摘要

胍丁胺是一种新型的神经调质,在几种细胞损伤模型中对中枢神经系统发挥保护作用。然而,在神经退行性疾病中,这些保护作用的机制还知之甚少。傅里叶变换红外(FTIR)光谱分析可检测无序细胞和组织中的生物分子变化。在本报告中,我们利用 FTIR 光谱来描述在鱼藤酮诱导的神经母细胞瘤样分化的 SH-SY5Y 细胞损伤中,胍丁胺的存在或不存在所引起的变化。FTIR 光谱的分析表明,鱼藤酮处理的细胞发生了显著变化,而在用胍丁胺(250 nM)预孵育后获得的 FTIR 光谱则显著降低了这些氧化还原变化,更接近于对照细胞。特别是,鱼藤酮损伤的细胞表现出与酰胺 I 相关的光谱变化,这对应于β-折叠成分的增加,以及酰胺 II 吸收强度的降低,表明 N-H 弯曲和 C-N 伸缩的丧失。傅里叶自卷积分析也证明了这些变化。因此,鱼藤酮诱导的与蛋白质羧基基团相关的伸缩振动带水平的增加将导致细胞中存在大量错误折叠的蛋白质。胍丁胺能有效地减轻鱼藤酮对蛋白质结构的这些影响。总之,胍丁胺的抗氧化和清除自由基特性降低了鱼藤酮引起的细胞损伤程度,达到蛋白质结构水平。这些,连同其他先前的观察结果,证明了胍丁胺在治疗帕金森病方面的治疗潜力。

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