@article {2420,
	title = {Amyloid beta-peptide disrupts mitochondrial membrane lipid and protein structure: protective role of tauroursodeoxycholate},
	journal = {Biochem Biophys Res Commun},
	volume = {281},
	number = {2},
	year = {2001},
	note = {<p>0006-291X (Print)0006-291X (Linking)Journal ArticleResearch Support, Non-U.S. Gov{\textquoteright}t</p>
},
	month = {Feb 23},
	pages = {468-74},
	abstract = {<p>Mitochondria have been implicated in the cytotoxicity of amyloid beta-peptide (A beta), which accumulates as senile plaques in the brain of Alzheimer{\textquoteright}s disease patients. Tauroursodeoxycholate (TUDC) modulates cell death, in part, by preventing mitochondrial membrane perturbation. Using electron paramagnetic resonance spectroscopy analysis of isolated mitochondria, we tested the hypothesis that A beta acts locally in mitochondrial membranes to induce oxidative injury, leading to increased membrane permeability and subsequent release of caspase-activating factors. Further, we intended to determine the role of TUDC at preventing A beta-induced mitochondrial membrane dysfunction. The results demonstrate oxidative injury of mitochondrial membranes during exposure to A beta and reveal profound structural changes, including modified membrane lipid polarity and disrupted protein mobility. Cytochrome c is released from the intermembrane space of mitochondria as a consequence of increased membrane permeability. TUDC, but not cyclosporine A, almost completely abrogated A beta-induced perturbation of mitochondrial membrane structure. We conclude that A beta directly induces cytochrome c release from mitochondria through a mechanism that is accompanied by profound effects on mitochondrial membrane redox status, lipid polarity, and protein order. TUDC can directly suppress A beta-induced disruption of the mitochondrial membrane structure, suggesting a neuroprotective role for this bile salt.</p>
},
	keywords = {Amyloid beta-Peptides/*pharmacology, Animals, Cytochrome c Group/drug effects/metabolism, Electron Spin Resonance Spectroscopy, Intracellular Membranes/chemistry/*drug effects/metabolism, Membrane Lipids/chemistry/*metabolism, Membrane Proteins/chemistry/*drug effects/metabolism, Mitochondria, Liver/drug effects, Mitochondria/drug effects, Oxidative Stress, Peptide Fragments/pharmacology, Permeability/drug effects, Rats, Rats, Wistar, Spin Labels, Taurochenodeoxycholic Acid/*pharmacology},
	url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve\&db=PubMed\&dopt=Citation\&list_uids=11181071 },
	author = {Rodrigues, C. M. and Sola, S. and Brito, M. A. and Brondino, C. D. and Brites, D. and Moura, J. J.}
}
