RATIONALE: Previous fluorescence studies employing 1,6-diphenyl-1,3,5-hexatriene (DPH) have revealed an increase in the fluidity of platelet membranes from individuals with Alzheimer's disease (AD) and their first-degree relatives. This biophysical alteration has been reported to be relatively specific for the hydrocarbon core of platelet membranes, where DPH preferentially localizes; this effect is not reflected by the fluorescent reporter triethylamino-DPH, which labels membranes at the lipid-aqueous interface. OBJECTIVE: The goal of this study was to explore the validity and reproducibility of these findings using an independent biophysical technique, electron spin resonance (ESR) spectroscopy. METHODS: Platelet membranes prepared from first-degree relatives of patients with AD were labeled with DPH, or the spin-labeled fatty acid probes 5-doxylstearate (5-DS) and 12-doxylstearate (12-DS). These spin labeled probes provide an index of structural order at the respective depths of their nitroxide moieties in the membrane. The resulting preparations were examined by fluorescence and ESR spectroscopy. RESULTS: Increased platelet membrane fluidity (PMF), as determined by the fluorescence anisotropy of DPH, was associated with only a modest reduction in the order parameter derived for 5-DS labeled membranes. In contrast, the mean order parameters derived from the paired samples labeled with 12-DS differed substantially from each other, and revealed decreased order (increased fluidity) in the hydrocarbon 12-C region where DPH preferentially localizes. CONCLUSIONS: These results provide an independent validation of the biophysical alterations of platelet membranes that are manifested by a subgroup of patients with AD and their first-degree relatives.
RATIONALE: Previous fluorescence studies employing 1,6-diphenyl-1,3,5-hexatriene (DPH) have revealed an increase in the fluidity of platelet membranes from individuals with Alzheimer's disease (AD) and their first-degree relatives. This biophysical alteration has been reported to be relatively specific for the hydrocarbon core of platelet membranes, where DPH preferentially localizes; this effect is not reflected by the fluorescent reporter triethylamino-DPH, which labels membranes at the lipid-aqueous interface. OBJECTIVE: The goal of this study was to explore the validity and reproducibility of these findings using an independent biophysical technique, electron spin resonance (ESR) spectroscopy. METHODS: Platelet membranes prepared from first-degree relatives of patients with AD were labeled with DPH, or the spin-labeled fatty acid probes 5-doxylstearate (5-DS) and 12-doxylstearate (12-DS). These spin labeled probes provide an index of structural order at the respective depths of their nitroxide moieties in the membrane. The resulting preparations were examined by fluorescence and ESR spectroscopy. RESULTS: Increased platelet membrane fluidity (PMF), as determined by the fluorescence anisotropy of DPH, was associated with only a modest reduction in the order parameter derived for 5-DS labeled membranes. In contrast, the mean order parameters derived from the paired samples labeled with 12-DS differed substantially from each other, and revealed decreased order (increased fluidity) in the hydrocarbon 12-C region where DPH preferentially localizes. CONCLUSIONS: These results provide an independent validation of the biophysical alterations of platelet membranes that are manifested by a subgroup of patients with AD and their first-degree relatives.
Authors: Emma M Woodcock; Paul Girvan; Julia Eckert; Ismael Lopez-Duarte; Markéta Kubánková; Jack J W A van Loon; Nicholas J Brooks; Marina K Kuimova Journal: Biophys J Date: 2019-04-08 Impact factor: 4.033
Authors: Tamás Kálai; Jitka Petrlova; Mária Balog; Hnin Hnin Aung; John C Voss; Kálmán Hideg Journal: Eur J Med Chem Date: 2011-02-03 Impact factor: 6.514