PKA-Rap1a dependent regulation of AGE-RAGE signaling in type II diabetes mellitus |
Posted on:2017-08-11 | Degree:M.S | Type:Thesis |
University:Mississippi State University | Candidate:Worsham, Rebecca Anne | Full Text:PDF |
GTID:2454390008490971 | Subject:Molecular biology |
Abstract/Summary: | |
Type II diabetes mellitus is associated with many detrimental health situations including heart complications. The purpose of this study was to identify a role for PKA-dependent Rap1a signaling in the AGE-RAGE cascade. My hypothesis was Rap1a GTPase increased the downstream effects of AGE-RAGE signaling in diabetes via a PKA-dependent pathway leading to elevated ECM remodeling in the heart. Cardiac fibroblasts were isolated from heterozygous (Het) and diabetic (db/db) mice. To test the hypothesis, gain-of-function and loss-of-function treatments were used. PKC-Zeta is known as a major signaling hub that potentially links PKA-dependent and AGE-RAGE signaling cascades so PKC-Zeta inhibition to downregulate PKA-dependent cascade at PKC-Zeta was also used. Results showed a downregulation of signaling markers in the AGE-RAGE cascade when disrupting Rap1a crosstalk at PKC-Zeta. By understanding where the PKA-dependent and AGE-RAGE signaling cascades crosstalk, a new molecular mechanism is understood possibly leading to decreasing remodeling in a diabetic heart. |
Keywords/Search Tags: | II diabetes mellitus, Type II, AGE-RAGE signaling |
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