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SARS-CoV-2 spike S1 subunit protein-mediated increase of beta-secretase 1 (BACE1) impairs human brain vessel cells.
Choi, Ji-Young; Park, Jung Hyun; Jo, Chulman; Kim, Kyung-Chang; Koh, Young Ho.
  • Choi JY; Division of Brain Disease Research, Department of Chronic Disease Convergence Research, Korea National Institute of Health, Cheongju-si, Chungcheongbuk-do, 28159, South Korea.
  • Park JH; Division of Brain Disease Research, Department of Chronic Disease Convergence Research, Korea National Institute of Health, Cheongju-si, Chungcheongbuk-do, 28159, South Korea.
  • Jo C; Division of Brain Disease Research, Department of Chronic Disease Convergence Research, Korea National Institute of Health, Cheongju-si, Chungcheongbuk-do, 28159, South Korea.
  • Kim KC; Division of Emerging Virus and Vector Research, Korea National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju-si, Chungchengbuk-do, 28159, South Korea.
  • Koh YH; Division of Brain Disease Research, Department of Chronic Disease Convergence Research, Korea National Institute of Health, Cheongju-si, Chungcheongbuk-do, 28159, South Korea. Electronic address: kohyoungho122@gmail.com.
Biochem Biophys Res Commun ; 626: 66-71, 2022 10 20.
Article in English | MEDLINE | ID: covidwho-1966379
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 ß-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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Cardiovascular Diseases / COVID-19 Limits: Animals / Humans Language: English Journal: Biochem Biophys Res Commun Year: 2022 Document Type: Article Affiliation country: J.bbrc.2022.07.113

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Cardiovascular Diseases / COVID-19 Limits: Animals / Humans Language: English Journal: Biochem Biophys Res Commun Year: 2022 Document Type: Article Affiliation country: J.bbrc.2022.07.113