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

• Main Authors: Andrea Valeri, Luigi Chiricosta, Valeria Calcaterra, Mara Biasin, Gioia Cappelletti, Stephana Carelli, Gian Vincenzo Zuccotti, Placido Bramanti, Gloria Pelizzo, Emanuela Mazzon, Agnese Gugliandolo
• Format: Article
• Language: English
• Published: MDPI AG 2021-08-01
• Series: Cells
• Subjects: oxidative stress; ROS homeostasis; cell cycle; apoptosis; HCN-2; SARS-CoV-2
• Online Access: https://www.mdpi.com/2073-4409/10/9/2189

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 <i>TXN</i> gene, resulting in deregulation of its antioxidant functions, as well as a decrease in the DNA-repairing mechanism, as indicated by the decrease in <i>KAT5</i>. Western blot analyses of SOD1 and iNOS confirmed the impairment of reduction mechanisms and an increase in oxidative stress. Upregulation of <i>CDKN2A</i> and a decrease in <i>CDK4</i> and <i>CDK6</i> 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 <i>PMAIP1</i> 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.