Date of Award
Fall 11-16-2011
Degree Type
Thesis
Degree Name
Master of Science (MS)
Department
Biology
First Advisor
Chun Jiang
Second Advisor
Ritu Aneja
Third Advisor
Andrew Clancy
Abstract
Diabetes mellitus is characterized by hyperglycemia, oxidative stress and excessive production of intermediary metabolites including methylglyoxal (MGO), a reactive carbonyl. MGO can readily interact with proteins, lipids and DNA, and cause an imbalance of the cellular antioxidant system leading to carbonyl stress. The effects of MGO can be devastating if the targeted molecules are responsible for the maintenance of membrane potentials and ionic homeostasis. Here we show that MGO disrupts the vascular isoform of ATP-sensitive K+ (KATP) channels by acting on the mRNAs of Kir6.1 and SUR2B subunits thereby regulating vascular tone. Our results show that the 3’ untranslated region (UTR) of Kir6.1 mRNA and the coding region of SUR2B mRNA are targeted by MGO causing a disruption of vascular KATP channels. The destabilization of the mRNAs of KATP channel can in turn affect K+ homeostasis of vascular smooth muscles as well as vascular responses to circulating vasodilators and vasoconstrictors.
DOI
https://doi.org/10.57709/2356616
Recommended Citation
Konduru, Anuhya S., "The Reactive Carbonyl Methylglyoxal Suppresses Vascular KATP Channels by MRNA Destabilization." Thesis, Georgia State University, 2011.
doi: https://doi.org/10.57709/2356616