diphenylhexatriene and Disease-Models--Animal

The presynaptic protein alpha-synuclein, implicated in Parkinson disease (PD), binds phospholipids and has a role in brain fatty acid (FA) metabolism. In mice lacking alpha-synuclein (Snca-/-), total brain steady-state mass of the mitochondria-specific phospholipid, cardiolipin, is reduced 22% and its acyl side chains show a 51% increase in saturated FAs and a 25% reduction in essential n-6, but not n-3, polyunsaturated FAs. Additionally, 23% reduction in phosphatidylglycerol content, the immediate biosynthetic precursor of cardiolipin, was observed without alterations in the content of other brain phospholipids. Consistent with these changes, more ordered lipid head group and acyl chain packing with enhanced rotational motion of diphenylhexatriene (DPH) about its long axis were demonstrated in time-resolved DPH fluorescence lifetime experiments. These abnormalities in mitochondrial membrane properties were associated with a 15% reduction in linked complex I/III activity of the electron transport chain, without reductions in mitochondrial number, complex II/III activity, or individual complex I, II, III, or IV activity. Reduced complex I activity is thought to be a critical factor in the development of PD. Thus, altered membrane composition and structure and impaired complex I/III function in Snca-/- brain suggest a relationship between alpha-synuclein's role in brain lipid metabolism, mitochondrial function, and PD.

Topics: alpha-Synuclein; Animals; Arachidonic Acid; Blotting, Western; Brain; Cardiolipins; Cell Membrane; Diphenylhexatriene; Disease Models, Animal; Electrophoresis, Gel, Two-Dimensional; Electrophoresis, Polyacrylamide Gel; Fatty Acids; Female; Kinetics; Lipids; Male; Mice; Mice, Transgenic; Mitochondria; Neurons; Palmitic Acid; Parkinson Disease; Phosphatidylglycerols; Phospholipids; Reverse Transcriptase Polymerase Chain Reaction; Spectrometry, Fluorescence; Time Factors

To study membrane viscosity in various rat strains with genetic forms of experimental hypertension.. The relationship between blood pressure and membrane dynamics was investigated in erythrocytes from three different rat strains with experimental hypertension, namely two models of salt-induced hypertension (Sabra and Dahl rats) and Lyon hypertensive rats with spontaneous hypertension.. Membrane microviscosity was evaluated by diphenylhexatriene and trimethylamino-diphenylhexatriene fluorescence steady-state anisotropy.. There were no significant differences among particular experimental groups in trimethylamino-diphenylhexatriene anisotropy that reflect microviscosity changes at the water-lipid interface of the external membrane leaflet. In contrast, the diphenylhexatriene anisotropy, which is related to the core membrane microviscosity, was significantly reduced in the Dahl salt-sensitive rats (irrespective of salt intake level) and in the Sabra hypertension-prone rats with developed salt hypertension. Erythrocyte membranes of Lyon hypertensive rats also had lower values of diphenylhexatriene anisotropy than the respective normotensive controls but this difference was not statistically significant.. Systolic (and often also diastolic) blood pressure correlated negatively with the diphenylhexatriene anisotropy in each of the three strains studied, whereas the trimethylamino-diphenylhexatriene anisotropy of the erythrocyte membranes had no significant relationship to the blood pressure. Further experiments should clarify whether the observed relationship of the diphenylhexatriene anisotropy to blood pressure reflects true pathogenetic mechanisms or is a consequence of haemodynamic changes.

Topics: Animals; Blood Pressure; Diphenylhexatriene; Disease Models, Animal; Erythrocyte Membrane; Fluorescence Polarization; Fluorescent Dyes; Hypertension; In Vitro Techniques; Male; Membrane Fluidity; Rats; Rats, Inbred Strains; Sodium Chloride; Viscosity