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Enhanced cholesterol accessibility for PFO interaction in membranes containing POPE and POPS phospholipids.

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dc.contributor.advisor London, Erwin en_US
dc.contributor.author Lee, Caroline en_US
dc.contributor.other Department of Biochemistry and Cell Biology en_US
dc.date.accessioned 2013-05-22T17:35:01Z
dc.date.accessioned 2015-04-24T14:46:59Z
dc.date.available 2013-05-22T17:35:01Z
dc.date.available 2015-04-24T14:46:59Z
dc.date.issued 2011-12-01 en_US
dc.identifier Lee_grad.sunysb_0771M_10803 en_US
dc.identifier.uri http://hdl.handle.net/1951/59752 en_US
dc.identifier.uri http://hdl.handle.net/11401/71315 en_US
dc.description 47 pg. en_US
dc.description.abstract Cholesterol biosynthesis regulation via the SREBP (sterol regulatory element binding protein) pathway has previously been elucidated to exhibit a switch-like response in the ER at ~ 5 mol% cholesterol. It has been proposed that this threshold value is mainly due to the control of the concentration at which cholesterol becomes accessible by the phospholipid composition of the ER membrane. We have conducted experiments to investigate this hypothesis. Perfringolysin O (PFO) was applied as a sterol sensor that binds membranes and oligomerizes upon cholesterol exposure in artificial membranes. Using this system, we detected a progressive enhancement of cholesterol accessibility as more PE (phosphatidylethanolamine) and PS (phosphatidylserine) phospholipids were incorporated into SUVs composed of PC (phosphatidylcholine). Further studies involving the uptake of various biologically relevant fatty intercalants (triglycerides, diglycerides, fatty alcohols) into PE/PS-containing vesicles reduced the threshold to a value as low as 2 mol% cholesterol. We discuss the hypothetical contributions of PE, PS, and various fatty intercalants in lowering the threshold concentration at which the SREBP pathway decides to transcriptionally activate or deactivate cholesterol biosynthesis. en_US
dc.description.sponsorship This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree. en_US
dc.format Monograph en_US
dc.format.medium Electronic Resource en_US
dc.language.iso en_US en_US
dc.publisher The Graduate School, Stony Brook University: Stony Brook, NY. en_US
dc.subject.lcsh Biochemistry en_US
dc.title Enhanced cholesterol accessibility for PFO interaction in membranes containing POPE and POPS phospholipids. en_US
dc.type Thesis en_US
dc.mimetype Application/PDF en_US
dc.contributor.committeemember Brown, Deborah A en_US

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