DOI
https://doi.org/10.25772/XEWH-WK10
Defense Date
2009
Document Type
Thesis
Degree Name
Master of Science
Department
Pharmacology & Toxicology
First Advisor
Hamid Akbarali
Abstract
Tyrosine nitration results in altered function of smooth muscle voltage-gated L-type calcium channel. We explored the possibility that smooth muscle contains denitrase activity to allow functional recovery of the calcium channel without requiring synthesis of new channel proteins. Following peroxynitrite treatment of mouse colonic smooth muscle strips, CaCl2 (1 mM)-induced smooth muscle contraction was significantly reduced by 67% (P ≤ 0.05), which reversed by approximately 86% upon periodic washing within 2 hr period (P ≤ 0.001). The effect of the c-Src kinase inhibitor, PP2, on muscle contraction was also restored after 2 hr post-peroxynitrite treatment consistent with the thesis that recovery from tyrosine nitration allows for tyrosine phosphorylation of the calcium channel. In addition, sodium orthovanadate prevented nitration-induced inhibition of muscle contraction by approximately 90%. Moreover, denitration of nitrated proteins was observed by western blots in smooth muscle cells over 2 hr. Since nitrotyrosine formation interferes with tyrosine kinase pathways involved in cell signaling, the presence of denitrase activity in smooth muscle cells may have profound and important effects in restoring the function of nitrated proteins involved in cell signaling processes.
Rights
© The Author
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
December 2009