G_h partially mediates α₁-adrenergic receptor-stimulated cardiac hypertrophy independent of G_q Regulation

In cardiac myocytes, stimulation of α1-adrenoceptor(α1-AR) leads to hypertrophic phenomenon. The G_h protein is tissue type transglutaminase and transmits the intracellular signal with GTPase activity. Little is known about G_h-mediated intracellular signal transductions to develop the hypertrophy. The aim of this study was to elucidate how G _h mediates norepinephrine(NE)-stimulated intracellular signal transductions leading to the hypertrophic responses in neonatal rat cardiomyocytes. NE-induced protein/DNA ratio and ERKs activation were inhibited by a α1-AR blocker(prazosin), but not by a β,-AR blocker(propranolol) . G_q mainly regulated protein/DNA ratio and genetic markers of hypertrophy but inhibition of G_q did not induce a decrease of hypertrophic response to the normal control. The treatment with siRNA for G _h suppressed NE-induced PKC/MEK1, 2/ERKs activation. NE-induced β-MHC reorganization was inhibited by small interfering RNA targeting G_q or G_h. Cell surface area level of G_q inhibition was not the same as control but atrial natriuretic peptide(ANP), a cardiac hypertrophy marker, was inhibited by G_h and G_q suppression and coincidently inhibition of both G_h and G_q reduced the gene expression. These findings suggest that G_h is partially involved in the hypertrophic response induced by NE in cardiomyocytes through PKC/MEK1, 2/ERKs signal pathways via α1-AR/G_h.