Colchicine Protects against Ethanol-Induced Senescence and Senescence-Associated Secretory Phenotype in Endothelial Cells

Huakang Zhou; Dilaware Khan; Norbert Gerdes; Carsten Hagenbeck; Majeed Rana; Jan Frederick Cornelius; Sajjad Muhammad

doi:10.3390/antiox12040960

Colchicine Protects against Ethanol-Induced Senescence and Senescence-Associated Secretory Phenotype in Endothelial Cells

Antioxidants (Basel). 2023 Apr 19;12(4):960. doi: 10.3390/antiox12040960.

Authors

Huakang Zhou¹, Dilaware Khan¹, Norbert Gerdes², Carsten Hagenbeck³, Majeed Rana⁴, Jan Frederick Cornelius¹, Sajjad Muhammad^{1

5}

Affiliations

¹ Department of Neurosurgery, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine-University Düsseldorf, 40225 Düsseldorf, Germany.
² Division of Cardiology, Pulmonology and Vascular Medicine, University Hospital and Medical Faculty, Heinrich-Heine-University, 40225 Düsseldorf, Germany.
³ Clinic for Gynecology and Obstetrics, University Clinic, 40225 Düsseldorf, Germany.
⁴ Department of Oral, Maxillofacial and Facial Plastic Surgery, University Hospital Düsseldorf, Moorenstrasse 5, 40225 Düsseldorf, Germany.
⁵ Department of Neurosurgery, University Hospital Helsinki, Topeliuksenkatu 5, 00260 Helsinki, Finland.

Abstract

Inflammaging is a potential risk factor for cardiovascular diseases. It results in the development of thrombosis and atherosclerosis. The accumulation of senescent cells in vessels causes vascular inflammaging and contributes to plaque formation and rupture. In addition to being an acquired risk factor for cardiovascular diseases, ethanol can induce inflammation and senescence, both of which have been implicated in cardiovascular diseases. In the current study, we used colchicine to abate the cellular damaging effects of ethanol on endothelial cells. Colchicine prevented senescence and averted oxidative stress in endothelial cells exposed to ethanol. It lowered the relative protein expression of aging and senescence marker P21 and restored expression of the DNA repair proteins KU70/KU80. Colchicine inhibited the activation of nuclear factor kappa B (NFκ-B) and mitogen activated protein kinases (MAPKs) in ethanol-treated endothelial cells. It reduced ethanol-induced senescence-associated secretory phenotype. In summary, we show that colchicine ameliorated the ethanol-caused molecular events, resulting in attenuated senescence and senescence-associated secretory phenotype in endothelial cells.

Keywords: HUVECs; MAPKs; NFκ-B; SASP; cellular senescence; colchicine; ethanol; inflammation.

Grants and funding

The current study was supported by Forschungskommission HHU Düsseldorf, Stiftung Neurochirurgische Forschung (DGNC), EANS Research Funds, BMBF, to S. Muhammad and by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) Grant No. 397484323–CRC/TRR259; project A05 to N. Gerdes.