According to the neurological symptoms of SARS-CoV-2 infection, it is known that the nervous system is influenced by the virus. We used pediatric human cerebral cortical cell line HCN-2 as a neuronal model of SARS-CoV-2 infection, and, through transcriptomic analysis, our aim was to evaluate the effect of SARS-CoV-2 in this type of cells. Transcriptome analyses revealed impairment in TXN gene, resulting in deregulation of its antioxidant functions, as well as a decrease in the DNA-repairing mechanism, as indicated by the decrease in KAT5. Western blot analyses of SOD1 and iNOS confirmed the impairment of reduction mechanisms and an increase in oxidative stress. Upregulation of CDKN2A and a decrease in CDK4 and CDK6 point to the blocking of the cell cycle that, according to the deregulation of repairing mechanism, has apoptosis as the outcome. A high level of proapoptotic gene PMAIP1 is indeed coherent with neuronal death, as also supported by increased levels of caspase 3. The upregulation of cell-cycle-blocking genes and apoptosis suggests a sufferance state of neurons after SARS-CoV-2 infection, followed by their inevitable death, which can explain the neurological symptoms reported. Further analyses are required to deeply explain the mechanisms and find potential treatments to protect neurons from oxidative stress and prevent their death.

Transcriptomic analysis of HCN-2 cells suggests connection among oxidative stress, senescence, and neuron death after SARS-CoV-2 infection / A. Valeri, L. Chiricosta, V. Calcaterra, M. Biasin, G. Cappelletti, S. Carelli, G.V. Zuccotti, P. Bramanti, G. Pelizzo, E. Mazzon, A. Gugliandolo. - In: CELLS. - ISSN 2073-4409. - 10:9(2021 Aug 25), pp. 2189.1-2189.15. [10.3390/cells10092189]

Transcriptomic analysis of HCN-2 cells suggests connection among oxidative stress, senescence, and neuron death after SARS-CoV-2 infection

M. Biasin;G. Cappelletti;G.V. Zuccotti;G. Pelizzo;
2021-08-25

Abstract

According to the neurological symptoms of SARS-CoV-2 infection, it is known that the nervous system is influenced by the virus. We used pediatric human cerebral cortical cell line HCN-2 as a neuronal model of SARS-CoV-2 infection, and, through transcriptomic analysis, our aim was to evaluate the effect of SARS-CoV-2 in this type of cells. Transcriptome analyses revealed impairment in TXN gene, resulting in deregulation of its antioxidant functions, as well as a decrease in the DNA-repairing mechanism, as indicated by the decrease in KAT5. Western blot analyses of SOD1 and iNOS confirmed the impairment of reduction mechanisms and an increase in oxidative stress. Upregulation of CDKN2A and a decrease in CDK4 and CDK6 point to the blocking of the cell cycle that, according to the deregulation of repairing mechanism, has apoptosis as the outcome. A high level of proapoptotic gene PMAIP1 is indeed coherent with neuronal death, as also supported by increased levels of caspase 3. The upregulation of cell-cycle-blocking genes and apoptosis suggests a sufferance state of neurons after SARS-CoV-2 infection, followed by their inevitable death, which can explain the neurological symptoms reported. Further analyses are required to deeply explain the mechanisms and find potential treatments to protect neurons from oxidative stress and prevent their death.
oxidative stress; ROS homeostasis; cell cycle; apoptosis; HCN-2; SARS-CoV-2
Settore BIO/13 - Biologia Applicata
Settore MED/04 - Patologia Generale
CAR_EXT20MBIAS_01 - Characterization of SARS-CoV-2 accessory proteins in terms of host adaptation, biochemical properties, and pharmacophore models (CORONA) - BIASIN, MARA - CAR_EXT - CARIPLO - EXTRABANDO E PROGETTI TERRITORIALI - 2020
RL_DG-WEL20MBIAS_01 - Caratterizzazione delle sequenze codificanti di SARS-CoV-2 e valutazione del loro ruolo nella patogenesi di COVID-19 - BIASIN, MARA - RL_DG-WEL - Bandi DG Welfare - 2020
25-ago-2021
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/863807
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