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Gp130 cytokines stimulate proteasomal degradation of tyrosine hydroxylase in sympathetic neurons
Author(s) -
Shi Xiao,
Habecker Beth A
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.576.9
Subject(s) - glycoprotein 130 , medicine , myocardial infarction , tyrosine hydroxylase , endocrinology , ventricle , leukemia inhibitory factor , cytokine , proinflammatory cytokine , sympathetic nervous system , heart failure , chemistry , cardiology , interleukin 6 , inflammation , dopamine , blood pressure
Alterations in cardiac sympathetic transmission after myocardial infarction contribute to ventricular arrhythmias and sudden cardiac death. Tyrosine hydroxylase (TH) content, the rate‐limiting enzyme in norepinephrine synthesis, is depleted in the left ventricle after myocardial infarction, but elevated in other parts of heart. At the same time that TH content per nerve fiber is decreased, inflammatory cytokines including leukemia inhibitory factor, cardiotrophin‐1 and interleukin 6 are elevated in the damaged ventricle after myocardial infarction. These cytokines signal through the gp130 receptor complex, and preliminary data in cultured sympathetic neurons suggests that activation of gp130 stimulates TH degradation. We used cultured sympathetic neurons to investigate the effect of gp130 cytokines on TH content. Inhibiting proteasome activity by lactacystin prevented cytokine‐induced TH protein loss in cultured sympathetic neurons. These data suggest that gp130 cytokines have a direct effect on TH protein stability, providing a potential mechanism for the local depletion of TH in the left ventricle after myocardial infarction. Additional preliminary data suggest the absence of gp130 receptor in sympathetic neurons prevented depletion of TH protein in the left ventricle after myocardial infarction. Supported by: Steinberg graduate Fellowship (XS), NIH HL68321 (BAH)