دورية أكاديمية
أعرض في EDS

Targeting ATP2B1 impairs PI3K/Akt/FOXO signaling and reduces SARS-COV-2 infection and replication.

التفاصيل البيبلوغرافية
العنوان: Targeting ATP2B1 impairs PI3K/Akt/FOXO signaling and reduces SARS-COV-2 infection and replication.
المؤلفون: de Antonellis P; CEINGE Biotecnologie Avanzate, Naples, 80145, Italy.; Dipartimento di Medicina Molecolare e Biotecnologie Mediche (DMMBM), 'Federico II' University of Naples, Naples, 80131, Italy.; Elysium Cell Bio Ita SRL, Via Gaetano Salvatore 486, 80145, Naples, Italy., Ferrucci V; CEINGE Biotecnologie Avanzate, Naples, 80145, Italy.; Dipartimento di Medicina Molecolare e Biotecnologie Mediche (DMMBM), 'Federico II' University of Naples, Naples, 80131, Italy.; Elysium Cell Bio Ita SRL, Via Gaetano Salvatore 486, 80145, Naples, Italy., Miceli M; CEINGE Biotecnologie Avanzate, Naples, 80145, Italy., Bibbo F; CEINGE Biotecnologie Avanzate, Naples, 80145, Italy.; Dipartimento di Medicina Molecolare e Biotecnologie Mediche (DMMBM), 'Federico II' University of Naples, Naples, 80131, Italy., Asadzadeh F; CEINGE Biotecnologie Avanzate, Naples, 80145, Italy.; Dipartimento di Medicina Molecolare e Biotecnologie Mediche (DMMBM), 'Federico II' University of Naples, Naples, 80131, Italy.; European School of Molecular Medicine, SEMM, Naples, Italy., Gorini F; Dipartimento di Medicina Molecolare e Biotecnologie Mediche (DMMBM), 'Federico II' University of Naples, Naples, 80131, Italy., Mattivi A; Armenise-Harvard Laboratory of Cell Division, Department of Cellular Computational and Integrative Biology-CIBIO, University of Trento, Trento, Italy., Boccia A; CEINGE Biotecnologie Avanzate, Naples, 80145, Italy., Russo R; CEINGE Biotecnologie Avanzate, Naples, 80145, Italy.; Dipartimento di Medicina Molecolare e Biotecnologie Mediche (DMMBM), 'Federico II' University of Naples, Naples, 80131, Italy., Andolfo I; CEINGE Biotecnologie Avanzate, Naples, 80145, Italy.; Dipartimento di Medicina Molecolare e Biotecnologie Mediche (DMMBM), 'Federico II' University of Naples, Naples, 80131, Italy., Lasorsa VA; CEINGE Biotecnologie Avanzate, Naples, 80145, Italy., Cantalupo S; CEINGE Biotecnologie Avanzate, Naples, 80145, Italy., Fusco G; Istituto Zooprofilattico Sperimentale del Mezzogiorno, Naples, 80055, Italy., Viscardi M; Istituto Zooprofilattico Sperimentale del Mezzogiorno, Naples, 80055, Italy., Brandi S; Istituto Zooprofilattico Sperimentale del Mezzogiorno, Naples, 80055, Italy., Cerino P; Istituto Zooprofilattico Sperimentale del Mezzogiorno, Naples, 80055, Italy., Monaco V; CEINGE Biotecnologie Avanzate, Naples, 80145, Italy.; Department of Chemical Sciences, University 'Federico II' University of Naples, Naples, 80125, Italy., Choi DR; Department of Surgery, Yonsei University College of Medicine, Seoul, Korea.; Elysiumbio Inc., #2007, Samsung Cheil B/D, 309, Teheran-ro, Gangnam-gu, Seoul, 06151, Korea., Cheong JH; Department of Surgery, Yonsei University College of Medicine, Seoul, Korea., Iolascon A; CEINGE Biotecnologie Avanzate, Naples, 80145, Italy.; Dipartimento di Medicina Molecolare e Biotecnologie Mediche (DMMBM), 'Federico II' University of Naples, Naples, 80131, Italy., Amente S; Dipartimento di Medicina Molecolare e Biotecnologie Mediche (DMMBM), 'Federico II' University of Naples, Naples, 80131, Italy., Monti M; CEINGE Biotecnologie Avanzate, Naples, 80145, Italy.; Department of Chemical Sciences, University 'Federico II' University of Naples, Naples, 80125, Italy., Fava LL; Armenise-Harvard Laboratory of Cell Division, Department of Cellular Computational and Integrative Biology-CIBIO, University of Trento, Trento, Italy., Capasso M; CEINGE Biotecnologie Avanzate, Naples, 80145, Italy.; Dipartimento di Medicina Molecolare e Biotecnologie Mediche (DMMBM), 'Federico II' University of Naples, Naples, 80131, Italy., Kim HY; Elysiumbio Inc., #2007, Samsung Cheil B/D, 309, Teheran-ro, Gangnam-gu, Seoul, 06151, Korea., Zollo M; CEINGE Biotecnologie Avanzate, Naples, 80145, Italy. massimo.zollo@unina.it.; Dipartimento di Medicina Molecolare e Biotecnologie Mediche (DMMBM), 'Federico II' University of Naples, Naples, 80131, Italy. massimo.zollo@unina.it.; Elysium Cell Bio Ita SRL, Via Gaetano Salvatore 486, 80145, Naples, Italy. massimo.zollo@unina.it.; European School of Molecular Medicine, SEMM, Naples, Italy. massimo.zollo@unina.it.; DAI Medicina di Laboratorio e Trasfusionale, 'Federico II' University of Naples, 80131, Naples, Italy. massimo.zollo@unina.it.
المصدر: EMBO reports [EMBO Rep] 2024 Jul; Vol. 25 (7), pp. 2974-3007. Date of Electronic Publication: 2024 May 30.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 100963049 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1469-3178 (Electronic) Linking ISSN: 1469221X NLM ISO Abbreviation: EMBO Rep Subsets: MEDLINE
أسماء مطبوعة: Publication: 2024- : [London] : Nature Publishing Group
Original Publication: Oxford, UK : Published for EMBO by Oxford University Press, 2000-
مواضيع طبية MeSH: SARS-CoV-2*/drug effects , SARS-CoV-2*/physiology , Virus Replication*/drug effects , Proto-Oncogene Proteins c-akt*/metabolism , COVID-19*/virology , COVID-19*/metabolism , Signal Transduction*/drug effects , Phosphatidylinositol 3-Kinases*/metabolism , Calcium*/metabolism, Humans ; Animals ; Forkhead Box Protein O3/metabolism ; Forkhead Box Protein O3/genetics ; Chlorocebus aethiops ; COVID-19 Drug Treatment ; Vero Cells ; Female ; Calcium-Transporting ATPases/metabolism ; Calcium-Transporting ATPases/genetics ; Male
مستخلص: ATP2B1 is a known regulator of calcium (Ca 2+ ) cellular export and homeostasis. Diminished levels of intracellular Ca 2+ content have been suggested to impair SARS-CoV-2 replication. Here, we demonstrate that a nontoxic caloxin-derivative compound (PI-7) reduces intracellular Ca 2+ levels and impairs SARS-CoV-2 infection. Furthermore, a rare homozygous intronic variant of ATP2B1 is shown to be associated with the severity of COVID-19. The mechanism of action during SARS-CoV-2 infection involves the PI3K/Akt signaling pathway activation, inactivation of FOXO3 transcription factor function, and subsequent transcriptional inhibition of the membrane and reticulum Ca 2+ pumps ATP2B1 and ATP2A1, respectively. The pharmacological action of compound PI-7 on sustaining both ATP2B1 and ATP2A1 expression reduces the intracellular cytoplasmic Ca 2+ pool and thus negatively influences SARS-CoV-2 replication and propagation. As compound PI-7 lacks toxicity in vitro, its prophylactic use as a therapeutic agent against COVID-19 is envisioned here.
(© 2024. The Author(s).)
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معلومات مُعتمدة: D64I200003800 Regione Campania; Grant IG no. 22129 Fondazione AIRC per la ricerca sul cancro ETS (AIRC); 2017FNZRN3 Ministero dell'Istruzione, dell'Università e della Ricerca (MIUR); NRF 2018R1A5A2025079 Ministry of Science and ICT, South Korea (MSIT)
فهرسة مساهمة: Keywords: ATP2B1; Ca2+; PI3K/Akt/FOXO; SARS-CoV-2; Transcription
المشرفين على المادة: EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
SY7Q814VUP (Calcium)
0 (Forkhead Box Protein O3)
0 (FOXO3 protein, human)
EC 7.2.2.10 (Calcium-Transporting ATPases)
تواريخ الأحداث: Date Created: 20240530 Date Completed: 20240711 Latest Revision: 20240714
رمز التحديث: 20240714
مُعرف محوري في PubMed: PMC11239940
DOI: 10.1038/s44319-024-00164-z
PMID: 38816514
قاعدة البيانات: MEDLINE
الوصف
تدمد:1469-3178
DOI:10.1038/s44319-024-00164-z