The abuse of mixed or combined performance-enhancing drugs is widespread among athletes and amateurs, adults and adolescents. Clinical studies demonstrated that misuse of these doping agents is associated with serious adverse effects to many organs in human. Previously, we demonstrated in human peripheral lymphocytes (PBL) that high doses of anabolic androgenic steroids (AASs), like dihydrotestosterone (DHT) and growth factors, such as insulin-like growth factor-1 (IGF-1), have effects at gene and protein levels. Supraphysiological treatments of DHT and IGF-1 affected the expression of genes involved in skeletal muscle disorders as well as in cell-mediated immunological response. At protein level, DHT hyperdosage affects cell motility and apoptosis; IGF-1 hyperstimulation triggers an active cytoskeletal reorganization and an overproduction of immune response- and inflammation-related cytokines. In this study, we investigate the combined effects of DHT and IGF-1 hyperdosage in PBL using a differential proteomic approach. DHT and IGF-1 combined treatment affects cell adhesion, migration and survival through modulation of expression levels of cytokines and paxillin signaling-related proteins, and activation of several pathways downstream FAK. Our results indicate a synergistic effect of DHT and IGF-1 which has potential implications for health risk factors. This article is protected by copyright. All rights reserved.
Synergistic effect of DHT and IGF-1 hyperstimulation in human peripheral blood lymphocytes
IMPERLINI, Esther;SPAZIANI, SARA;MANCINI, Annamaria;BUONO, Pasqualina;ORRU', STEFANIA
2015-01-01
Abstract
The abuse of mixed or combined performance-enhancing drugs is widespread among athletes and amateurs, adults and adolescents. Clinical studies demonstrated that misuse of these doping agents is associated with serious adverse effects to many organs in human. Previously, we demonstrated in human peripheral lymphocytes (PBL) that high doses of anabolic androgenic steroids (AASs), like dihydrotestosterone (DHT) and growth factors, such as insulin-like growth factor-1 (IGF-1), have effects at gene and protein levels. Supraphysiological treatments of DHT and IGF-1 affected the expression of genes involved in skeletal muscle disorders as well as in cell-mediated immunological response. At protein level, DHT hyperdosage affects cell motility and apoptosis; IGF-1 hyperstimulation triggers an active cytoskeletal reorganization and an overproduction of immune response- and inflammation-related cytokines. In this study, we investigate the combined effects of DHT and IGF-1 hyperdosage in PBL using a differential proteomic approach. DHT and IGF-1 combined treatment affects cell adhesion, migration and survival through modulation of expression levels of cytokines and paxillin signaling-related proteins, and activation of several pathways downstream FAK. Our results indicate a synergistic effect of DHT and IGF-1 which has potential implications for health risk factors. This article is protected by copyright. All rights reserved.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
