Bradykinin prevents the apoptosis of NIT-1 cells induced by TNF-α via the PI3K/Akt and MAPK signaling pathways

Abstract

The kallikrein-kinin system (KKS) is a complex multi-enzyme system which is composed of circulating and tissue kallikrein and kinin. It is well established that tissue kallikrein and kinin play crucial and diverse roles in cardiovascular and renal homeostasis. Recent data indicate that kallikrein gene delivery reduces insulin resistance in STZ-treated rats suggesting a protective role for kinin in the development of diabetes. This study investigated the effects of exogenous bradykinin (BK) on the apoptosis of NIT-1 cells, a pancreatic β-cell line in vitro. Exogenous BK significantly protected NIT-1 cells from TNF-α-induced apoptosis. These effects were associated with upregulation of Bcl-2 and Bcl-xL protein expression levels as well as with downregulation of Bax expression levels via the activation of the mitogen-activated protein kinase and PI3K/Akt signaling pathways. In conclusion, these data highlight the beneficial roles of BK on pancreatic β-cell function.