Year: 2022
Type: article
Abstract: Clinical 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.
Source: Viruses
DOI: 10.3390/v14050983
Institutions: Temple University, Rowan University
Language: English
Subfield: Clinical Biochemistry
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,513
Awards: G1887331173, G2032689579, G205906573, G2063062577, PGC-1alpha and Reelin: new players in HAND progression., Involvement of HIV-1 Vpr in neuronal degeneration., G2259460779, G2472043511, G3759531860, G3879172005, G4175053134, G4181814922, G4311777926, G485702183, G5841172106, G5861894894, G6225135965, G6421342166, G6435066781, G6520826913, G6916049380, G6921594822, G6978112581, G7142370777, Role of microRNA in HIV associated neurological disorder (HAND)., G7846369273, G7868800806, G864959716
OpenAlex ID: W4229377585