Akt Specific Activator SC79 Protects against Early Brain Injury following Subarachnoid Hemorrhage

Abstract

A growing body of evidence demonstrates that Akt may serve as a therapeutic target for treatment of early brain injury following subarachnoid hemorrhage (SAH). The purpose of the current study was to evaluate the neuroprotective effect of Akt specific activator SC79 in an experimental rat model of SAH. SAH was induced by injecting 300 μL of blood into the prechiasmatic cistern. Intracerebroventricular (ICV) injection of SC79 (30 min post-SAH) induced the p-Akt (Ser473) expression in a dose-dependent manner. A single ICV dose treatment of SC79 (100 μg/rat) significantly increased the expression of Bcl-2 and p-GSK-3β (Ser9), decreased the protein levels of Bax, cytoplasm cytochrome c, and cleaved caspase-3, indicating the antiapoptotic effect of SC79. As a result, the number of apoptotic cells was reduced 24 h post SAH. Moreover, SC79 treatment alleviated SAH-induced oxidative stress, restored mitochondrial morphology, and improved neurological deficits. Strikingly, treatment of SC79 provided a beneficial outcome against neurologic deficit with a therapeutic window of at least 4 h post SAH by ICV injection and 30 min post SAH by intraperitoneal injection. Collectively, SC79 exerts its neuroprotective effect likely through the dual activities of antioxidation and antiapoptosis. These data provide a basic platform to consider SC79 as a novel therapeutic agent for treatment of SAH.

Perfluorooctanesulfonate (PFOS)-induced Sertoli cell injury through a disruption of F-actin and microtubule organization is mediated by Akt1/2

“…The selected concentrations of PFOS used in our experiments were based on earlier studies 13, 23, 77 , and were earlier shown to have no detectable cytotoxicity in Sertoli cells 13 . The concentration of SC79 used in our studies was similar to earlier studies on mammalian cells and tissues both in vitro and in vivo without cytotoxicity 39, 78 .…”

Protective Effects the Akt Activator SC79 in Hepatic Ischemia-Reperfusion Injury

“…Increasing evidence shows that activation of PI3K/Akt signaling has important biological functions in protecting against H/R-induced cell injury [26]. Thus, activation of PI3K/Akt signaling becomes a primary goal of therapeutic intervention for liver protection against I/R injury.…”

“…SC79 is a novel and safe small-molecule compound, which can be used as a selective, highly-efficient, and cell-permeable Akt activator [13]. It protects against early brain injuries through the dual activities of antioxidation and antiapoptosis [26]. In addition, SC79 has proved to have no significant adverse effects in experimental studies in mice and human cells [13].…”

“…Cytoprotective effects have been shown in experimental ischemia-elicited neuronal death [13], early brain injury [14], retinal pigment epithelium cells from UV radiation [15], and myocardiocytes from oxygen and glucose deprivation (OGD)/reoxygenation in vitro [16], but fails to reduce myocardial I/R injury [17], which was contrast to previous studies with genetic models of cardiac Akt overexpression [18,19]. It is unclear whether SC79 has a protective effect on hepatocytes or liver tissues after ischemia-reperfusion injury.…”

SC79 protects dopaminergic neurons from oxidative stress

“…For instance, SC79 was shown to inhibit excitotoxicity and to alleviate stroke-induced neuronal cell death [ 14 ]. SC79 administration in vivo could also alleviate early brain injuries [ 18 ]. Interestingly, a recent study however demonstrated that SC79 was in-effective to protect rat heart from ischemic injuries [ 20 ].…”