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AKT Activator SC79 Protects Hepatocytes From TNF-α-mediated Apoptosis and Alleviates d-Gal/LPS-induced Liver Injury

AKT Activator SC79 Protects Hepatocytes From TNF-α-mediated Apoptosis and Alleviates d-Gal/LPS-induced Liver Injury

Zhen-Tang Jing, Wei Liu, Chao-Rong Xue, Shu-Xiang Wu, Wan-Nan Chen, Xin-Jian Lin, Xu Lin

Am J Physiol Gastrointest Liver Physiol. 2019 Mar 1;316(3):G387-G396.

PMID: 30629471

Abstract:

Tumor necrosis factor-α (TNF-α) is a highly pleiotropic cytokine executing biological functions as diverse as cell proliferation, metabolic activation, inflammatory responses, and cell death. TNF-α can induce multiple mechanisms to initiate apoptosis in hepatocytes leading to the subsequent liver injury. Since the phosphoinositide-3-kinase/protein kinase B (PI3K/Akt) pathway is known to have a protective role in death factor-mediated apoptosis, it is our hypothesis that activation of Akt may represent a therapeutic strategy to alleviate TNF-α-induced hepatocyte apoptosis and liver injury. We report here that the Akt activator SC79 protects hepatocytes from TNF-α-induced apoptosis and protects mice from d-galactosamine (d-Gal)/lipopolysaccharide (LPS)-induced TNF-α-mediated liver injury and damage. SC79 not only enhances the nuclear factor-κB (NF-κB) prosurvival signaling in response to TNF-α stimulation, but also increases the expression of cellular FLICE (FADD-like IL-1β-converting enzyme)-inhibitory protein L and S (FLIPL/S), which consequently inhibits the activation of procaspase-8. Furthermore, pretreatment of the PI3K/Akt inhibitor LY294002 reverses all the SC79-induced hepatoprotective effects. These results strongly indicate that SC79 protects against TNF-α-induced hepatocyte apoptosis and suggests that SC79 is likely a promising therapeutic agent for ameliorating the development of liver injury. NEW & NOTEWORTHY SC79 protects hepatocytes from TNF-α-mediated apoptosis and mice from Gal/LPS-induced liver injury and damage. Cytoprotective effects of SC79 against TNF-α act through both AKT-mediated activation of NF-κB and upregulation of FLIPL/S.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP305834791	SC79		305834-79-1	Price

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