ABSTRACT
SARS-CoV-2 is an emerging viral pathogen and a major global public health challenge since December of 2019, with limited effective treatments throughout the pandemic. As part of the innate immune response to viral infection, type I interferons (IFN-I) trigger a signaling cascade that culminates in the activation of hundreds of genes, known as interferon stimulated genes (ISGs), that collectively foster an antiviral state. We report here the identification of a group of type I interferon suppressed genes, including fatty acid synthase (FASN), which are involved in lipid metabolism. Overexpression of FASN or the addition of its downstream product, palmitate, increased viral infection while knockout or knockdown of FASN reduced infection. More importantly, pharmacological inhibitors of FASN effectively blocked infections with a broad range of viruses, including SARS-CoV-2 and its variants of concern. Thus, our studies not only suggest that downregulation of metabolic genes may present an antiviral strategy by type I interferon, but they also introduce the potential for FASN inhibitors to have a therapeutic application in combating emerging infectious diseases such as COVID-19.
ABSTRACT
Objective To investigate the effect of fatty acid synthase (FASN)on apoptosis in pancreatic cancer cell PANC-1 and the possible molecular mechanism.Methods Annexin V/FITC and flow cytometry were performed to detect the expression of FASN in pancreatic cancer PANC-1 after C75 treatment and the change of apoptosis in pancreatic cancer cell PANC-1 treated with C75.Quantity reverse transcriptase polymerase chain reaction (RT-PCR)and Western blot were used to measure the protein and RNA expressions of Caspase-3,bcl-2 and FASN.Results Inhibited by C75,the activity of FASN in pancreatic cancer cell PANC-1 was significantly decreased.Meanwhile,PANC-1 showed an increased apoptosis level in a dose-dependent manner (P < 0.05 ). Furthermore,after C75 inhibited FASN in pancreatic cancer cells,the protein and RNA expressions of Caspase-3 significantly increased (P <0.05)whereas the level of Bcl-2 reduced (P <0.05).Conclusion FASN is involved in the process of apoptosis in PANC-1 via Bcl-2 and Caspase-3.Therefore,FASN will provide a new target for the treatment of pancreatic cancer and generate better treatment efficacy.
ABSTRACT
Fatty acid synthase is the key enzyme which catalyzes the de novo synthesis of long-chain fatty acids from acetyl-CoA and malonyl-CoA.Only recently has it been appreciated that C75,the inhibitor of fatty acid synthase can make mice lose weight via reducing food intake and increasing energy consumption.The present paper reviews the potential mechanism by which the inhibitor of fatty acid synthase may influence the expression of hypothalamic neuropeptides mediating the behaviour of food intake in central nervous system and decrease adipose sediment or increase energy production.