Abnormal lipid profile of dystrophic cardiac tissue as demonstrated by one- and two-dimensional magic-angle spinning 1H NMR spectroscopy
Abnormal lipid profile of dystrophic cardiac tissue as demonstrated by one- and two-dimensional magic-angle spinning 1H NMR spectroscopy
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DOI：
10.1002/mrm.1185
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发表时间：
2001-08-01
影响因子：
3.3
通讯作者：
Nicholson, JK
中科院分区：
文献类型：
--
作者：
Griffin, JL;Williams, HJ;Nicholson, JK
肌营养不良蛋白是一种与肌膜和细胞膜相关的蛋白质，在杜氏肌营养不良症（DMD）患者或mdx小鼠中不表达。DMD是一种致命的疾病，其中相当大比例的死亡与心力衰竭相关（类似于40%患有扩张型心肌病，并且在死亡时> 90%具有临床显著的心脏缺陷）。在这项研究中，完整的营养不良的心脏组织的代谢组成进行了研究，使用高分辨率魔角旋转（HRMAS）H-1 NMR光谱与1-和2D脉冲序列加上模式识别（PR）。虽然传统的溶剂预饱和光谱表明在脂质中的CH 2链长的增加，PR相关光谱（COSY）光谱分析表明，这也是伴随着乳酸或苏氨酸的浓度增加沿着在这些脂质中的CH = CHCH 2CO基团的相对减少。为了研究这些脂质的物理环境，在全组织样品上获得T-2和扩散加权H-1 MAS NMR光谱。营养不良组织中脂质信号强度的相对增加是由于具有长T-2和短扩散速率的分子的增加。一系列脉冲程序的使用允许直接探测脂质浸润发生的生化环境，并通过将实验与PR结合，还评估了脂质浸润和积累的意义。(C)2001 Wiley-Liss，Inc.
Dystrophin, a protein associated with sarcolemma and cell membranes, is not expressed in sufferers of Duchenne muscular dystrophy (DMD), or in the mdx mouse. DMD is a fatal disorder, with a significant proportion of fatalities associated with cardiac failure (similar to 40% having dilated cardiomyopathy and > 90% clinically significant cardiac defects at death). In this study, the metabolic composition of intact dystrophic cardiac tissue was investigated using high-resolution magic-angle spinning (HRMAS) H-1 NMR spectroscopy with both 1- and 2D pulse sequences coupled with pattern recognition (PR). While conventional solvent presaturation spectra indicated increases in CH2 chain length in lipids, PR analysis of correlation spectroscopy (COSY) spectra demonstrated that this was also accompanied by an increase in concentration of lactate or threonine along with a relative decrease in CH = CHCH2CO groups in these lipids. To investigate the physical environment of these lipids, T-2- and diffusion-weighted H-1 MAS NMR spectra were acquired on whole-tissue samples. The relatively increased lipid signal intensity in dystrophic tissue was due to an increase in molecules with long T-2 and short diffusion rates. The use of a range of pulse programs allowed the direct probing of the biochemical environment in which the lipid infiltration occurred, and by coupling the experiments to PR the significance of lipid infiltration and accumulation was also assessed. (C) 2001 Wiley-Liss, Inc.