Abnormal lipid profile of dystrophic cardiac tissue as demonstrated by one- and two-dimensional magic-angle spinning (1)H NMR spectroscopy.
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 ( approximately 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) (1)H NMR spectroscopy with both 1- and 2D pulse sequences coupled with pattern recognition (PR). While conventional solvent presaturation spectra indicated increases in CH(2) 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 = CHCH(2)CO groups in these lipids. To investigate the physical environment of these lipids, T(2)- and diffusion-weighted (1)H 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.
Griffin
J L
JL
Biological Chemistry, Biomedical Sciences, Imperial College of Science, Technology and Medicine, London, UK. j.griffin@ic.ac.uk
Williams
H J
HJ
Sang
E
E
Nicholson
J K
JK
D000818:Animals; D004195:Disease Models, Animal; D016189:Dystrophin / Q000378:metabolism; D016018:Least-Squares Analysis; D050356:Lipid Metabolism; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D020388:Muscular Dystrophy, Duchenne / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D012815:Signal Processing, Computer-Assisted
D016189:Dystrophin