Dokument: Rapalink-1 Attenuates Oxidative-Stress-Induced Senescence in Vascular Cells in Association with Reduced NF-κB and MAPK Signaling

Titel:	Rapalink-1 Attenuates Oxidative-Stress-Induced Senescence in Vascular Cells in Association with Reduced NF-κB and MAPK Signaling
URL für Lesezeichen:	https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=73842
URN (NBN):	urn:nbn:de:hbz:061-20260706-125616-3
Kollektion:	Publikationen
Sprache:	Englisch
Dokumententyp:	Wissenschaftliche Texte » Artikel, Aufsatz
Medientyp:	Text
Autoren:	You, Jinliang [Autor] Liu, Hongjun [Autor] Khan, Dilaware [Autor] Sahan, Sihmehmet [Autor] Faust, Katharina [Autor] Muhammad, Sajjad [Autor] Rana, Majeed [Autor]
Dateien:	[Dateien anzeigen] Adobe PDF [Details] 2,79 MB in einer Datei [ZIP-Datei erzeugen] Dateien vom 06.07.2026 / geändert 06.07.2026
Stichwörter:	mTOR , MAPK , Rapalink-1 , oxidative stress , SASP , NF-κB , vascular senescence
Beschreibung:	Oxidative stress contributes to vascular dysfunction and senescence-associated changes through activation of inflammatory and stress-responsive signaling pathways. Although the mammalian target of rapamycin (mTOR) integrates metabolic and redox-related signals, its role in vascular stress responses remains incompletely understood. In this study, we investigated the effects of Rapalink-1, an mTOR inhibitor, on H2O2-induced injury responses in human vascular endothelial cells (HUVECs) and vascular smooth muscle cells (SMCs). Oxidative stress-associated changes were assessed using oxidation-sensitive fluorescence, DNA damage markers (γ-H2AX and 8-OHDG), and senescence-associated readouts (SA-β-gal, Lamin B1, and p21). Senescence-associated secretory phenotype (SASP)-related factors were analyzed by qPCR and Western blot, and mTOR-, NF-κB-, and MAPK-related signaling was evaluated by Western blotting. H2O2 exposure reduced cell viability and increased oxidative stress-associated readouts, DNA damage markers, senescence-associated changes, and SASP-related factor expression in both HUVECs and SMCs. Rapalink-1 attenuated many of these responses, including oxidation-sensitive fluorescence, γ-H2AX and 8-OHDG staining, SA-β-gal positivity, Lamin B1 loss, p21 upregulation, and the expression of inflammatory and matrix-remodeling factors. These effects were accompanied by reduced phosphorylation of p65, p38, ERK1/2, S6, and 4EBP1. Overall, Rapalink-1 is associated with attenuation of oxidative stress-induced injury responses in vascular endothelial and smooth muscle cells, together with reduced NF-κB-, MAPK-, and mTOR-related signaling. These findings support further investigation of mTOR-targeted approaches in vascular aging and oxidative stress-related vascular dysfunction.
Rechtliche Vermerke:	Originalveröffentlichung: You, J., Liu, H., Khan, D., Rana, M., Sahan, S., Faust, K., & Muhammad, S. (2026). Rapalink-1 Attenuates Oxidative-Stress-Induced Senescence in Vascular Cells in Association with Reduced NF-κB and MAPK Signaling. Biology : Open Access Journal, 15(9), Article 732. https://doi.org/10.3390/biology15090732
Lizenz:	Dieses Werk ist lizenziert unter einer Creative Commons Namensnennung 4.0 International Lizenz
Fachbereich / Einrichtung:	Medizinische Fakultät
Dokument erstellt am:	06.07.2026
Dateien geändert am:	06.07.2026