Transcriptomic Analysis of HCN-2 Cells Suggests Connection among Oxidative Stress, Senescence, and Neuron Death after SARS-CoV-2 Infection

Cells

Gioia Cappelletti¹  Gloria Pelizzo¹  Mara Biasin¹  Gian Vincenzo Zuccotti²  Valeria Calcaterra²  Emanuela Mazzon³  Andrea Valeri³  Luigi Chiricosta³  Placido Bramanti³  Agnese Gugliandolo³  Stephana Carelli⁴ 

[1] Department of Biomedical and Clinical Sciences-L. Sacco, University of Milan, 20157 Milan, Italy;Department of Paediatrics, Ospedale dei Bambini “Vittore Buzzi”, 20154 Milano, Italy;IRCCS Centro Neurolesi “Bonino-Pulejo”, Via Provinciale Palermo, Contrada Casazza, 98124 Messina, Italy;Paediatric Clinical Research Center Fondazione Romeo ed Enrica Invernizzi, University of Milan, 20157 Milan, Italy;

关键词: oxidative stress;    ROS homeostasis;    cell cycle;    apoptosis;    HCN-2;    SARS-CoV-2;   

DOI  :  10.3390/cells10092189

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown