Colchicine prevents oxidative stress-induced endothelial cell senescence via blocking NF-κB and MAPKs: implications in vascular diseases.

IF 4.4 3区医学 Q2 IMMUNOLOGY

Journal of Inflammation-London Pub Date : 2023-11-24 DOI:10.1186/s12950-023-00366-7

Huakang Zhou, Dilaware Khan, Sajid Muhammad Hussain, Norbert Gerdes, Carsten Hagenbeck, Majeed Rana, Jan Frederick Cornelius, Sajjad Muhammad

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引用次数: 0

Abstract

Background: Smoking, alcohol abuse, and hypertension are - among others, potential risk factors for cardiovascular diseases. These risk factors generate oxidative stress and cause oxidative stress-induced DNA damage, resulting in cellular senescence and senescence-associated secretory phenotype (SASP). The SASP factors in feed-forward response exacerbate inflammation and cause tissue remodeling, resulting in atherosclerotic plaque formation and rupture.

Results: Colchicine inhibited ROS generation and mitigated oxidative stress-induced DNA damage. It dampened oxidative stress-induced endothelial cell senescence and improved the expression of DNA repair protein KU80 and aging marker Lamin B1. The drug attenuated the expression of senescence marker P21 at mRNA and protein levels. The pathway analysis showed that colchicine inhibited NF-κB and MAPKs pathways and subdued mTOR activation. Colchicine also attenuated mRNA expression of interleukin (IL)-1β, IL-6, IL-8, MCP-1, ICAM-1, and E-selectin. Furthermore, colchicine reduced the mRNA and protein expression of matrix metalloproteinase (MMP-2).

Conclusion: In summary, colchicine blocked oxidative stress-induced senescence and SASP by inhibiting the activation of NF-κB and MAPKs pathways.

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秋水仙碱通过阻断NF-κB和MAPKs阻止氧化应激诱导的内皮细胞衰老:在血管疾病中的意义

背景:吸烟、酗酒和高血压是心血管疾病的潜在危险因素。这些危险因素产生氧化应激并引起氧化应激诱导的DNA损伤，导致细胞衰老和衰老相关分泌表型(SASP)。前馈反应中的SASP因子加剧炎症，引起组织重塑，导致动脉粥样硬化斑块形成和破裂。结果:秋水仙碱可抑制活性氧的产生，减轻氧化应激引起的DNA损伤。抑制氧化应激诱导的内皮细胞衰老，提高DNA修复蛋白KU80和衰老标志物Lamin B1的表达。该药在mRNA和蛋白水平上减弱衰老标志物P21的表达。通路分析显示秋水仙碱抑制NF-κB和MAPKs通路，抑制mTOR活化。秋水仙碱还能降低白细胞介素(IL)-1β、IL-6、IL-8、MCP-1、ICAM-1和e -选择素的mRNA表达。此外，秋水仙碱还能降低基质金属蛋白酶(MMP-2) mRNA和蛋白的表达。结论:综上所述，秋水仙碱通过抑制NF-κB和MAPKs通路的激活来阻断氧化应激诱导的衰老和SASP。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Inflammation-London IMMUNOLOGY-

CiteScore

7.90

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： Journal of Inflammation welcomes research submissions on all aspects of inflammation. The five classical symptoms of inflammation, namely redness (rubor), swelling (tumour), heat (calor), pain (dolor) and loss of function (functio laesa), are only part of the story. The term inflammation is taken to include the full range of underlying cellular and molecular mechanisms involved, not only in the production of the inflammatory responses but, more importantly in clinical terms, in the healing process as well. Thus the journal covers molecular, cellular, animal and clinical studies, and related aspects of pharmacology, such as anti-inflammatory drug development, trials and therapeutic developments. It also considers publication of negative findings. Journal of Inflammation aims to become the leading online journal on inflammation and, as online journals replace printed ones over the next decade, the main open access inflammation journal. Open access guarantees a larger audience, and thus impact, than any restricted access equivalent, and increasingly so, as the escalating costs of printed journals puts them outside University budgets. The unrestricted access to research findings in inflammation aids in promoting dynamic and productive dialogue between industrial and academic members of the inflammation research community, which plays such an important part in the development of future generations of anti-inflammatory therapies.