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dc.contributor.authorVemula, Pradheepen_US
dc.date.accessioned2016-03-29T15:39:11Z
dc.date.available2016-03-29T15:39:11Z
dc.date.issued2014
dc.identifier.urihttps://hdl.handle.net/2144/15346
dc.description.abstractMitofusin 2 (MFN2), an outer mitochondrial membrane protein expressed in virtually all human tissues, is a multi-faceted protein known to affect mitochondrial morphology, metabolism, tethering, and movement as well as overall cell cycle progression. Most intriguing among its characteristics is its ability to bind to Ras and Raf, upstream effectors in the MAPK/ERK pathway. Conditional knockout (cKO) of renal proximal tubule MFN2 in vivo showed a post-ischemic protective effect. While the two day survival of control mice was only 28%, an unexpected 86% of the MFN2 cKO mice were alive at two days post-ischemia. This is likely explained by MFN2's ability to bind and sequester Ras at baseline. Because the MFN2 deficient mice did not sequester as much Ras, renal proximal tubule cells were able to proliferate at a greater rate and restore organ function more quickly. Immunoprecipitation studies confirm a strong interaction between Ras and MFN2 in resting cells but a weaker one immediately following ischemic insult, even in cells replete with MFN2. These results suggest that blocking the MFN2-Ras interaction may be a novel method to treat acute kidney injury. A small peptide mimicking Ras to block MFN2 could be feasible. This should grant ischemic tissue an increased propensity to regenerate healthy cells while leaving non-ischemic tissue completely unaffected. Such a therapeutic agent would be novel in the treatment of acute kidney injury and may have uses in other tissues as well due to MFN2's widespread expression profile.en_US
dc.language.isoen_US
dc.subjectMolecular biologyen_US
dc.subjectMitofusin 2en_US
dc.subjectAcute kidney injuryen_US
dc.subjectHyperplasia suppressor geneen_US
dc.titleManipulation of Mitofusin2/Ras interaction as a therapy for acute ischemic kidney injuryen_US
dc.typeThesis/Dissertationen_US
dc.date.updated2016-03-12T07:11:41Z
etd.degree.nameMaster of Scienceen_US
etd.degree.levelmastersen_US
etd.degree.disciplineMedical Sciencesen_US
etd.degree.grantorBoston Universityen_US


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