Thyroid hormone inhibits ERK phosphorylation in pressure overload-induced hypertrophied mouse hearts through a receptor-mediated mechanism

摘要: Pressure overload-induced cardiac hypertrophy results in a pathological type of with activation signaling cascades like the extracellular signal-regulated kinase (ERK) pathway, which promotes negative remodeling and decreased contractile function. In contrast, thyroid hormone mediates physiological resulting enhanced addition, action is diminished pressure hypertrophy. We hypothesized that status modulates ERK activity administration could alter this induced by overload. activated phosphorylation; accordingly, we investigated phosphorylation hearts control, hypothyroid, hyperthyroid mice. effect T3 treatment on hypertrophied from transverse aortic-constricted (TAC) mice was investigated. Results showed phosphorylated (p-ERK) 25% hypothyroid presented increased p-ERK 80%. TAC greater than fourfold increase compared control Interestingly, dramatically canceled TAC-induced (36% lower control). Raf-1 upstream pathway. 45% phospho-Raf-1 (Ser338). inhibited overload further p-Raf-1 (Ser338) 37%, control. Overexpression receptor-α cultured cardiomyocytes potentiated inhibitory phosphorylation. concluded has an Raf-1/ERK Furthermore, pathway receptor-dependent mechanism.