GP130 IS INVOLVED IN STRETCH-INDUCED MAP KINASE ACTIVATION IN CARDIACMYOCYTES

We have recently reported that mitogen activated protein kinase (MAP k inase) is activated by the stretch of the cultured cardiac myocytes in the angiotensin II deficient state in the angiotensinogen-deficient m ice (Atg-/-), suggesting that factors other than the cardiac renin-ang iotensin system are involved in the stretch-induced MAP kinase activat ion. We examined the contribution of cytokines using RX435, an anti-gp 130 antibody. Leukemia inhibitory factor, which is one of the cytokine s and has the common receptor subunit gp130, activated MAP kinase and the response was completely blocked by pretreatment of the Atg-/- card iac myocytes with RX435. RX435 pretreatment greatly reduced stretch-in duced activation of MAP kinase in Atg-l-cardiac myocytes. Interestingl y, the same results were obtained in the cardiac myocytes of control m ice. These results suggest that cytokine-gp130 may play a role in the stretch-induced MAP kinase activation independently of Ang II in cardi ac myocytes. (C) 1998 Academic Press.