Event Title

Inhibition of the Activity of Enzyme A in Rat Cardiomyocytes

Session Number

C04

Advisor(s)

William Marszalec, Northwestern University
J. Andrew Wasserstrom, Northwestern University

Location

B101

Start Date

28-4-2016 10:15 AM

End Date

28-4-2016 10:40 AM

Disciplines

Biology

Abstract

Heart failure, a chronic condition caused by the gradual degradation of the heart muscle over time, is one of the leading causes of death in America. Despite its prevalence, a cure has not been discovered, though palliative measures may be taken. It is speculated that heart failure is caused by the deterioration and loss of t-tubules in cardiomyocytes, which results from the increasing activity of enzyme A. We seek to develop a drug that will prevent the activation of the enzyme A, which will protect t-tubules. Inositol monophosphate (IP1)- specific enzyme-linked immunosorbent assays were performed to test the drug’s effectiveness. The levels of IP-1, the enzymatic metabolite of enzyme A’s activity, were measured when the mouse HL-1 cardiac cells were activated with endothelin and measured again after treated with the experimental compound. Images of the treated and untreated cells under a confocal microscope were analyzed to detect the level of deterioration and reparation of the t-tubules. Among the sixteen initial experimental compounds considered for testing, compounds 2 and 9 have shown 50% inhibition of the endothelin response at low concentrations, indicating definite potential to be developed into a medicinal drug.


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Apr 28th, 10:15 AM Apr 28th, 10:40 AM

Inhibition of the Activity of Enzyme A in Rat Cardiomyocytes

B101

Heart failure, a chronic condition caused by the gradual degradation of the heart muscle over time, is one of the leading causes of death in America. Despite its prevalence, a cure has not been discovered, though palliative measures may be taken. It is speculated that heart failure is caused by the deterioration and loss of t-tubules in cardiomyocytes, which results from the increasing activity of enzyme A. We seek to develop a drug that will prevent the activation of the enzyme A, which will protect t-tubules. Inositol monophosphate (IP1)- specific enzyme-linked immunosorbent assays were performed to test the drug’s effectiveness. The levels of IP-1, the enzymatic metabolite of enzyme A’s activity, were measured when the mouse HL-1 cardiac cells were activated with endothelin and measured again after treated with the experimental compound. Images of the treated and untreated cells under a confocal microscope were analyzed to detect the level of deterioration and reparation of the t-tubules. Among the sixteen initial experimental compounds considered for testing, compounds 2 and 9 have shown 50% inhibition of the endothelin response at low concentrations, indicating definite potential to be developed into a medicinal drug.