Amyloid-beta peptide induces temporal membrane biphasic changes in astrocytes through cytosolic phospholipase A2.
Oligomeric amyloid-beta peptide (Abeta) is known to induce cytotoxic effects and to damage cell functions in Alzheimer's disease. However, mechanisms underlying the effects of Abeta on cell membranes have yet to be fully elucidated. In this study, Abeta 1-42 (Abeta(42)) was shown to cause a temporal biphasic change in membranes of astrocytic DITNC cells using fluorescence microscopy of Laurdan. Abeta(42) made astrocyte membranes became more molecularly-disordered within the first 30 min to 1 h, but gradually changed to more molecularly-ordered after 3 h. However, Abeta(42) caused artificial membranes of vesicles made of rat whole brain lipid extract to become more disordered only. The trend for more molecularly-ordered membranes in astrocytes induced by Abeta(42) was abrogated by either an NADPH oxidase inhibitor, apocynin, or an inhibitor of cytosolic phospholipase A(2) (cPLA(2)), but not by an inhibitor of calcium-independent PLA(2) (iPLA(2)). Apocynin also suppressed the increased production of superoxide anions (O(2)(-)) and phosphorylation of cPLA(2) induced by Abeta(42). In addition, hydrolyzed products of cPLA(2), arachidonic acid (AA), but not lysophosphatidylcholine (LPC) caused astrocyte membranes to become more molecularly-ordered. These results suggest (1) a direct interaction of Abeta(42) with cell membranes making them more molecularly-disordered, and (2) Abeta(42) also indirectly makes membranes become more molecularly-ordered by triggering the signaling pathway involving NADPH oxidase and cPLA(2) in astrocytes.
Hicks
Jacob B
JB
Department of Biological Engineering, University of Missouri, Columbia, Missouri 65211, USA.
Lai
Yinzhi
Y
Sheng
Wenwen
W
Yang
Xiaoguang
X
Zhu
Donghui
D
Sun
Grace Y
GY
Lee
James C-M
JC
D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000201:enzymology*; D002462:Cell Membrane / Q000187:drug effects* / Q000201:enzymology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006868:Hydrolysis / Q000187:drug effects; D008567:Membranes, Artificial; D019255:NADPH Oxidases / Q000378:metabolism; D044367:Phase Transition / Q000187:drug effects*; D054510:Phospholipases A2, Cytosolic / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D055503:Protein Multimerization / Q000187:drug effects; D051381:Rats; D013481:Superoxides / Q000378:metabolism; D014020:Tissue Extracts
D016229:Amyloid beta-Peptides; D004791:Enzyme Inhibitors; D008567:Membranes, Artificial; D014020:Tissue Extracts; D013481:Superoxides; D019255:NADPH Oxidases; D054510:Phospholipases A2, Cytosolic