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Cobra Cardiotoxin from Naja mossambica mossambica Promotes Neurodegeneration by Targeting Mitochondria
Date
2014Type
ThesisDepartment
Chemistry
Degree Level
Honors Thesis
Degree Name
Chemistry
Abstract
Cobra cardiotoxin (CTX) is a basic, cationic protein with a highly conserved
structure that has been shown to colocalize to mitochondria in cells and induce
mitochondrial dysfunction. Since CTX is a positively charged protein, I hypothesize that
basic residues in CTX from Naja mossambica mossambica will interact with negatively
charged phospholipids in the mitochondrial membrane, specifically cardiolipin. CTX from
Naja naja mossambica (N. n. mossambica) was diluted and tested on fetal C57BL/6J mouse
cortical neurons and SH-SY5Y neuroblastoma. The lethal dose 50 (LD50) for each cell line
was examined using the lactate dehydrogenase (LDH) release assay. Confocal microscopy
confirmed cellular uptake of rhodamine-labeled CTX and colocalization to mitochondria
and, molecular dynamics showed cardiolipin as a target in a model membrane made of
phosphatidylcholine and CDL. Lastly, CTX induced significant decrease in total ATP
production, mitochondrial-derived ATP, basal and maximal oxygen consumption rates in
SH-SY5Y neuroblastoma.
Permanent link
http://hdl.handle.net/11714/554Additional Information
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