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dc.contributor.advisorScarabelli, Tiziano
dc.contributor.authorBalingit, Jerome
dc.date.accessioned2011-01-24T15:13:22Z
dc.date.available2011-01-24T15:13:22Z
dc.date.issued2011
dc.identifier.urihttp://hdl.handle.net/10920/19838
dc.descriptioniv, 27 p.en_US
dc.description.abstractSeveral types of drugs have been developed to prevent damage caused by ischemia-reperfusion in heart muscle cells. Oxygen deprivation, also called hypoxia is known to cause certain cellular damage to cells over long term occurrence. Reperfusion, or sudden return of blood supply to ischemic areas, causes even more damage because of free radical damage. One type of drug developed by scientists is sildenafil, now marketed as Viagra, an erectile dysfunction treatment. The original goal for the development of sildenafil was for cardioprotection against ischemia-reperfusion damage in human patients. Studies have shown that the autophagic pathway is involved in the cardioprotection of heart cells. It is not known if sildenafil works by directly affecting autophagy. In order to understand their interactions, we studied the effects of sildenafil on autophagy levels in cardiac muscle cells derived from the AT-1 mouse cardiomyocyte tumor lineage, designated as HL-1. We exposed cell cultures to hypoxic conditions of 0.5 percent atmospheric oxygen to mimic ischemic conditions using an oxycycler, and ran a control with conditions mimicking the environment of heart muscle cells in vivo. Both exposures lasted two hours, and Western blot analysis of autophagy marker LC3-II showed that cells under hypoxic conditions treated with sildenafil had decreased levels compared to cells in the control group. Western blot analysis was also conducted on levels of three autophagy inhibitors mTOR, ERK, and AKT, and enhancer AMPK. Cellular levels indicate that autophagy is actually reduced during hypoxic conditions. We conclude that sildenafil may not have a direct effect on the regulatory pathway of autophagy during its cardioprotective mechanisms.en_US
dc.description.sponsorshipDepartment of Internal Medicine and Pharmacology. Center for Heart and Vessel Preclinical Studies. Wayne State University School of Medicine. Wayne State University. Detroit, Michigan.
dc.format.mimetypeapplication/pdf
dc.language.isoen_USen_US
dc.publisherKalamazoo Collegeen_US
dc.relation.ispartofKalamazoo College Biology Senior Individualized Projects Collection
dc.relation.ispartofseriesSenior Individualized Projects. Biology;
dc.rightsU.S. copyright laws protect this material. Commercial use or distribution of this material is not permitted without prior written permission of the copyright holder.
dc.titleCardioprotective Measures of Sildenafil Against the Effects of Ischemia/Reperfusionen_US
dc.typeThesisen_US


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    This collection includes Senior Individualized Projects (SIP's) completed in the Biology Department. Abstracts are generally available to the public, but PDF files are available only to current Kalamazoo College students, faculty, and staff.

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