Alteration of Akt1-Gsk3β Signaling Pathway in Trauma Hemorrhagic Shock Patients

Abstract

Trauma hemorrhagic shock (THS) is a major cause of death and disability worldwide. It is the leading cause of death with or without sepsis in approximately 50% of patients. In THS, there is an incidence of cellular apoptosis, which contributes majorly to cellular dysfunction, organ failure, and mortality. The Akt (protein kinase B) isoform, Akt1, and glycogen synthase kinase 3β (Akt1-GSK3β) signaling pathway controls cell survival and apoptosis. Deleterious consequences of alteration of this signaling system might lead to inflammation, cytokine storm, and other diseases. Hence, in the present study, we investigated the role of this signaling system by measuring the phosphorylation levels of Akt1-GSK3β. Here, we demonstrated that the downregulation of pAkt1 and upregulation of pGSK3β in THS were significantly associated with the severity of the shock, apoptosis of immune cells, altered glucose metabolism, inflammation, cytokine storm, hemostasis, and acidosis, causing mortality with or without sepsis. For the first time, this study shows that a dysregulated pAkt1-GSK3β pathway causes contrasting cell fates in THS, leading to trauma pathology. Hence, the delineation and the implications of this signaling system may provide a new important target for the treatment of THS. In addition, Akt activation may become a potential strategy for increasing the survival rate following THS.