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PKA-Rap1A Dependent Regulation of Age-Rage Signaling in Type II Diabetes Mellitus

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-ofunction and loss-ofunction 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.

Identiferoai:union.ndltd.org:MSSTATE/oai:scholarsjunction.msstate.edu:td-4543
Date07 May 2016
CreatorsWorsham, Rebecca Anne
PublisherScholars Junction
Source SetsMississippi State University
Detected LanguageEnglish
Typetext
Formatapplication/pdf
SourceTheses and Dissertations

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