Ghrelin exhibits its biological effect through binding to the growth hormone secretagogue 1a receptor (GHS-R1a). Recently, it has been reported that ghrelin has an anti-apoptotic effect in several cell types. However, the molecule mechanisms underlying the anti-apoptotic effect of ghrelin remain poorly understood. In this study, we investigated the intracellular mechanisms responsible for anti-apoptotic effect of ghrelin on human umbilical vein endothelial cells (HUVEC). Treatment of HUVEC with ghrelin inhibited high glucose-induced cell apoptosis. Ghrelin stimulated the rapid phosphorylation of mammalian target of rapamycin (mTOR), P70S6K and S6. The GHS-R1a-specific antagonist [D-Lys3]-GHRP-6 abolished the anti-apoptotic effect and inhibited the activation of mTOR, P70S6K, S6 induced by ghrelin. Pretreatment of cells with specific inhibitor of mTOR blocked the anti-apoptotic effect of ghrelin. In addition, ghrelin protected HUVECs against high glucose induced apoptosis by increasing Bcl-2/Bax ratio. Taken together, our results demonstrate that ghrelin produces a protective effect on HUVECs through activating GHS-R1a and mTOR/P70S6K signaling pathway mediates the effect of ghrelin. These observations suggest that ghrelin may act as a survival factor in preventing HUVECs apoptosis caused by high glucose.
Ghrelin exhibits its biological effect through binding to the growth hormone secretagogue 1a receptor ( GHS - R1a ) . Recently , it has been reported that ghrelin has an anti - apoptotic effect in several cell types . However , the molecule mechanisms underlying the anti - apoptotic effect of ghrelin remain poorly understood . In this study , we investigated the intracellular mechanisms responsible for anti - apoptotic effect of ghrelin on human umbilical vein endothelial cells ( HUVEC ) . Treatment of HUVEC with ghrelin inhibited high glucose - induced cell apoptosis . Ghrelin stimulated the rapid phosphorylation of mammalian target of rapamycin ( mTOR ) , P70S6 K and S6 . The GHS - R1a - specific antagonist [ D - Lys3]-GHRP-6 abolished the anti - apoptotic effect and inhibited the activation of mTOR , P70S6 K , S6 induced by ghrelin . Pretreatment of cells with specific inhibitor of mTOR blocked the anti - apoptotic effect of ghrelin . In addition , ghrelin protected HUVECs against high glucose induced apoptosis by increasing Bcl-2/Bax ratio . Taken together , our results demonstrate that ghrelin produces a protective effect on HUVECs through activating GHS - R1a and mTOR / P70S6 K signaling pathway mediates the effect of ghrelin . These observations suggest that ghrelin may act as a survival factor in preventing HUVECs apoptosis caused by high glucose .
What does mTOR stands for?
What does mTOR stands for ?
mammalian target of rapamycin
mammalian target of rapamycin