Curcumol Suppresses CCF-Mediated Hepatocyte Senescence Through Blocking LC3B-Lamin B1 Interaction in Alcoholic Fatty Liver Disease.
Curcumol Suppresses CCF-Mediated Hepatocyte Senescence Through Blocking LC3B-Lamin B1 Interaction in Alcoholic Fatty Liver Disease.
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姜黄酚通过阻断酒精性脂肪肝病中 LC3B 与核纤层蛋白 B1 的相互作用来抑制 CCF 介导的肝细胞衰老
DOI：
10.3389/fphar.2022.912825
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发表时间：
2022
影响因子：
5.6
通讯作者：
Jin, Huanhuan
中科院分区：
文献类型：
--
作者：
Qi, Xiaoyu;Zheng, Shuguo;Ma, Mingyue;Lian, Naqi;Wang, Hongting;Chen, Lerong;Song, Anping;Lu, Chunfeng;Zheng, Shizhong;Jin, Huanhuan
关键词：
近年来的研究表明，肝细胞衰老在酒精性脂肪性肝病（AFLD）的发生发展中起重要作用，提示抑制肝细胞衰老可能是治疗AFLD的潜在策略。本研究探讨莪术醇对酒精性脂肪肝细胞衰老的影响及其机制。结果表明，莪术醇能够减少乙醇液体饲料喂养的小鼠肝脏和乙醇处理的LO 2细胞中的脂质沉积和损伤。体内和体外研究均表明，补充莪术醇可有效缓解乙醇诱导的细胞衰老，表现为衰老相关β-半乳糖苷酶（SA-β-gal）活性降低、衰老相关标志物p16和p21的表达下调以及端粒和端粒酶系统功能障碍。一致地，用莪术醇处理导致乙醇诱导的细胞质染色质片段（CCF）的形成和随后cGAS-STING的活化的显著抑制，导致衰老相关分泌表型（SASP）相关炎性因子分泌的显著减少。进一步的研究表明，莪术醇抑制CCF的形成可能是通过阻断LC 3B与核纤层蛋白B1的相互作用，维持核膜的完整性。综上所述，这些结果表明，莪术醇能够通过抑制肝细胞衰老来改善AFLD，这可能归因于其阻断LC 3B和核纤层蛋白B1相互作用以及随后的CCF-cGAS-STING途径的失活。这些发现表明莪术醇在治疗AFLD中有希望的用途。
Recent studies indicated that hepatocyte senescence plays an important role in the development of alcoholic fatty liver disease (AFLD), suggesting that inhibition of hepatocyte senescence might be a potential strategy for AFLD treatment. The present study investigated the effect of curcumol, a component from the root of Rhizoma Curcumae, on hepatocyte senescence in AFLD and the underlying mechanisms implicated. The results showed that curcumol was able to reduce lipid deposition and injury in livers of ethanol liquid diet-fed mice and in ethanol-treated LO2 cells. Both in vivo and in vitro studies indicated that supplementation with curcumol effectively alleviated ethanol-induced cellular senescence as manifested by a decrease in senescence-associated β-galactosidase (SA-β-gal) activity, a downregulated expression of senescence-related markers p16 and p21, and dysfunction of the telomere and telomerase system. Consistently, treatment with curcumol led to a marked suppression of ethanol-induced formation of cytoplasmic chromatin fragments (CCF) and subsequent activation of cGAS-STING, resulting in a significant reduction in senescence-associated secretory phenotype (SASP)-related inflammatory factors’ secretion. Further studies indicated that curcumol’s inhibition of CCF formation might be derived from blocking the interaction of LC3B with lamin B1 and maintaining nuclear membrane integrity. Taken together, these results indicated that curcumol was capable of ameliorating AFLD through inhibition of hepatocyte senescence, which might be attributed to its blocking of LC3B and lamin B1 interaction and subsequent inactivation of the CCF-cGAS-STING pathway. These findings suggest a promising use of curcumol in the treatment of AFLD.
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影响因子：
13.3
作者：
Huang, Yao-Huei;Yang, Pei-Ming;Chiu, Shu-Jun
通讯作者：
Chiu, Shu-Jun
DOI：
10.1038/nri3921
发表时间：
2015-12
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
21.3
作者：
Glück S;Guey B;Gulen MF;Wolter K;Kang TW;Schmacke NA;Bridgeman A;Rehwinkel J;Zender L;Ablasser A
通讯作者：
Ablasser A
影响因子：
7.4
作者：
Abdelmegeed, Mohamed A.;Banerjee, Atrayee;Jang, Sehwan;Yoo, Seong-Ho;Yun, Jun-Won;Gonzalez, Frank J.;Keshavarzian, Ali;Song, Byoung-Joon
通讯作者：
Song, Byoung-Joon
DOI：
10.1083/jcb.201212110
发表时间：
2013-07-08
期刊：
The Journal of cell biology
影响因子：
--
作者：
Ivanov A;Pawlikowski J;Manoharan I;van Tuyn J;Nelson DM;Rai TS;Shah PP;Hewitt G;Korolchuk VI;Passos JF;Wu H;Berger SL;Adams PD
通讯作者：
Adams PD