Dept. of Physiology and Pharmacology
Oregon Health & Science University
Tyrosine hydroxylase is the rate-limiting enzyme in norepinephrine synthesis, and its expression and activity are regulated by growth factor, ischemia, nerve activity and inflammation. For example, inflammatory cytokines acting through the gp130 receptor cause the local depletion of TH in cardiac sympathetic nerves after myocardial infarction, without lowering TH gene expression. However, the mechanism of this cytokine-induced TH protein loss remains unknown. In the first part of my thesis, I investigated whether cytokines increased TH degradation. Experiments in Chapter 2 showed for the first time that inflammatory cytokines can stimulate proteasomal degradation of TH in catecholaminergic neurons. I showed that gp130 cytokines decreased TH half-life in sympathetic neurons and neuroblastoma cells, suggesting an increase in TH protein turnover. I found that CNTF induced TH ubiquitination and stimulated TH proteasomal degradation. In addition, I also identified that ERK1/2 was required
School of Medicine
Shi, Xiao, "gp130 cytokines stimulate tyrosine hydroxylase proteasomal degradation and activity in sympathetic neurons" (2012). Scholar Archive. 923.