CPLA2: key enzyme for astroctytic cell membrane phase property change induced by abeta

Abstract

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] The interaction of amyloid beta peptide (A[beta]) and cell membrane is believed to be the basis of its biological function including its toxicity to neurons, thus it is important to understand how A[beta] affects cell membrane properties. Contradictory observations have been reported on A [beta]'s effect on membrane fluidity, possibly resulted from different target samples, distinct A[beta] types, A[beta] preparation procedure, various incubation time length and diverse testing techniques applied. Among all these variables, we suspect A[beta] treatment time length to be one of the most important factors that will affect the effect of A [beta] on cell membrane. Here, we reported an interesting time-dependent biphasic change pattern of DITNC cell membrane phase properties induced by oligomeric A[beta][subscript 1-42]. A novel membrane phase property marker - Laurdan was applied in our study to reveal not only the overall membrane phase changes but also specific local membrane phase properties. The role of phospholipase A[subscript 2] (PLA[subscript 2]) in the membrane phase property changes induced by oligomeric A[beta][subscript 1-42] has also been tested. Based on our experimental results, a model was proposed to explain the time dependent biphasic membrane phase property change phenomenon and how A[beta] affects cell membrane phase properties.