Tissue Transglutaminase Activates NF-kappaB Pathway in the Atherosclerotic Coronary Artery / 체질인류학회지

ABSTRACT

Molecular mechanism of nuclear factor-kappaB(NF-kappaB) in the atherosclerosis has been unclear. Recently, NF-kappaB activating function of tissue transglutaminase (tTGase), multifunctional calcium-dependent transamidation enzyme, have been reported in the various tissues like neuroglia. In this report, we investigated the immunoreactivity of tTGase at the human atherosclerotic coronary artery, and examined the effect of tTGase on the well-known proatherogenic NF-kappaB pathway using tTGase-overexpressed cells. Immunohistochemical studies on autopsy samples showed that immunoreactivity of tTGase was markedly elevated in the neointimal tissues of atherosclerotic coronary arteries with progression of disease. Immunohistochemical staining also demonstrated that phosphorylated I-kappaB was activated in the atherosclerotic vessel wall. In vitro study using rat cardiomyoblast (H9c2) and tTGase-overexpressed H9c2 showed that activated tTGase enhanced the phosphorylation of I-kappaB, and this activation was inhibited by tTGase specific inhibitors. These findings suggest that cytosolic tTGase may serve as an activator of NF-kappaB.