SARS-CoV-2 Causes Lung Inflammation through Metabolic Reprogramming and RAGE
AuthorAllen, Charles Nathan S.
Arjona, Sterling P.
Ghaleb, Lea J.
Llewellyn, Megan D.
SAWAYA, BASSEL E
GroupMolecular Studies of Neurodegenerative Diseases Lab
FELS Cancer Institute for Personalized Medicine
Cancer and Cell Biology
Permanent link to this recordhttp://hdl.handle.net/20.500.12613/8091
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AbstractClinical studies indicate that patients infected with SARS-CoV-2 develop hyperinflammation, which correlates with increased mortality. The SARS-CoV-2/COVID-19-dependent inflammation is thought to occur via increased cytokine production and hyperactivity of RAGE in several cell types, a phenomenon observed for other disorders and diseases. Metabolic reprogramming has been shown to contribute to inflammation and is considered a hallmark of cancer, neurodegenerative diseases, and viral infections. Malfunctioning glycolysis, which normally aims to convert glucose into pyruvate, leads to the accumulation of advanced glycation end products (AGEs). Being aberrantly generated, AGEs then bind to their receptor, RAGE, and activate several pro-inflammatory genes, such as IL-1b and IL-6, thus, increasing hypoxia and inducing senescence. Using the lung epithelial cell (BEAS-2B) line, we demonstrated that SARS-CoV-2 proteins reprogram the cellular metabolism and increase pyruvate kinase muscle isoform 2 (PKM2). This deregulation promotes the accumulation of AGEs and senescence induction. We showed the ability of the PKM2 stabilizer, Tepp-46, to reverse the observed glycolysis changes/alterations and restore this essential metabolic process.
CitationAllen, Charles N. S., Maryline Santerre, Sterling P. Arjona, Lea J. Ghaleb, Muna Herzi, Megan D. Llewellyn, Natalia Shcherbik, and Bassel E. Sawaya. 2022. "SARS-CoV-2 Causes Lung Inflammation through Metabolic Reprogramming and RAGE" Viruses 14, no. 5: 983. https://doi.org/10.3390/v14050983
Citation to related workMDPI
Has partViruses, Vol. 14
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