tetano
Editor, Senior Moderator
Biochem Biophys Res Commun
. 2022 Aug 4;626:66-71.
doi: 10.1016/j.bbrc.2022.07.113. Online ahead of print.
SARS-CoV-2 spike S1 subunit protein-mediated increase of beta-secretase 1 (BACE1) impairs human brain vessel cells
Ji-Young Choi[SUP] 1 [/SUP], Jung Hyun Park[SUP] 1 [/SUP], Chulman Jo[SUP] 1 [/SUP], Kyung-Chang Kim[SUP] 2 [/SUP], Young Ho Koh[SUP] 3 [/SUP]
Affiliations
Abstract
Increasing evidence suggests incomplete recovery of COVID-19 patients, who continue to suffer from cardiovascular diseases, including cerebral vascular disorders (CVD) and neurological symptoms. Recent findings indicate that some of the damaging effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, especially in the brain, may be induced by the spike protein, leading to the disruption of the initial blood-brain barrier (BBB). SARS-CoV-2-infected cells and animals exhibit age-dependent pathogenesis. In this study, we identified endothelial BACE1 as a critical mediator of BBB disruption and cellular senescence induced by the SARS-CoV-2 spike S1 subunit protein. Increased BACE1 in human brain microvascular endothelial cells (HBMVEC) decreases the levels of tight junction proteins, including ZO-1, occludin, and claudins. Moreover, BACE1 overexpression leads to the accumulation of p16 and p21, typical hallmarks of cellular senescence. Our findings show that the SARS-CoV-2 spike S1 subunit protein upregulated BACE1 expression in HBMVECs, causing endothelial leakage. In addition, the SARS-CoV-2 spike S1 subunit protein induced p16 and p21 expression, indicating BACE1-mediated cellular senescence, confirmed by β-Gal staining in HBMVECs. In conclusion, this study demonstrated that BACE1-mediated endothelial cell damage and senescence may be linked to CVD after COVID-19 infection.
Keywords: BACE1; Brain vessels; COVID-19; Cell senescence; SARS-CoV-2.
. 2022 Aug 4;626:66-71.
doi: 10.1016/j.bbrc.2022.07.113. Online ahead of print.
SARS-CoV-2 spike S1 subunit protein-mediated increase of beta-secretase 1 (BACE1) impairs human brain vessel cells
Ji-Young Choi[SUP] 1 [/SUP], Jung Hyun Park[SUP] 1 [/SUP], Chulman Jo[SUP] 1 [/SUP], Kyung-Chang Kim[SUP] 2 [/SUP], Young Ho Koh[SUP] 3 [/SUP]
Affiliations
- PMID: 35970046
- DOI: 10.1016/j.bbrc.2022.07.113
Abstract
Increasing evidence suggests incomplete recovery of COVID-19 patients, who continue to suffer from cardiovascular diseases, including cerebral vascular disorders (CVD) and neurological symptoms. Recent findings indicate that some of the damaging effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, especially in the brain, may be induced by the spike protein, leading to the disruption of the initial blood-brain barrier (BBB). SARS-CoV-2-infected cells and animals exhibit age-dependent pathogenesis. In this study, we identified endothelial BACE1 as a critical mediator of BBB disruption and cellular senescence induced by the SARS-CoV-2 spike S1 subunit protein. Increased BACE1 in human brain microvascular endothelial cells (HBMVEC) decreases the levels of tight junction proteins, including ZO-1, occludin, and claudins. Moreover, BACE1 overexpression leads to the accumulation of p16 and p21, typical hallmarks of cellular senescence. Our findings show that the SARS-CoV-2 spike S1 subunit protein upregulated BACE1 expression in HBMVECs, causing endothelial leakage. In addition, the SARS-CoV-2 spike S1 subunit protein induced p16 and p21 expression, indicating BACE1-mediated cellular senescence, confirmed by β-Gal staining in HBMVECs. In conclusion, this study demonstrated that BACE1-mediated endothelial cell damage and senescence may be linked to CVD after COVID-19 infection.
Keywords: BACE1; Brain vessels; COVID-19; Cell senescence; SARS-CoV-2.