JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2014
·
IF 3.107
Huan Rao,Li-Xin Ma,Ting-Ting Xu,Jing Li,Ze-Yuan Deng,Ya-Wei Fan,Hong-Yan Li
Our previous study showed that trans-fatty acids can cause apoptosis of endothelial cells through the caspase pathway and the mitochondrial pathway. The objective of this study was to explore how trans-fatty acids activate the caspase pathway, whether there exist specific receptors induced apoptosis by comparing normal cells and non-rafts cells treated with elaidic acid (9t18:1) and oleic acid (9c18:1), respectively. Compared to normal cells treated with 9t18:1, the cell viability increased by 13% and the number of apoptotic cells decreased by 3% in non-rafts cells treated with 9t18:1 (p < 0.05), and the expression levels of pro-apoptotic proteins such as caspase-3, -8, -9, Bax, and Bid decreased, and expression of antiapoptotic protein Bcl-2 increased (p < 0.05). In addition, Fas/FasL expression in cell membrane decreased significantly (p < 0.05). In conclusion, the lipid rafts and Fas/FasL pathway may involve in 9t18:1-induced apoptosis of human umbilical vein endothelial cells.
研究领域:
细胞生物学
·
分子生物学
·
心血管研究
✓ 已验证
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2023
·
IF 4.3
Jing Lu,Ziheng Chen,Xiujuan Bu,Shanshan Chen,Shuang Guan
Elaidic acid (EA, C18:1 trans) is a kind of principal Trans fatty acid (TFA) and is widely found in processed food. Pyroptosis is a form of programmed cell death , distinct from apoptosis and traditional necrosis. Excessive pyroptosis could induce body injury and serious inflammation. However, the effect of EA on pyroptosis has not been reported. In the study, we found that EA exposure caused liver damage and hepatocyte pyroptosis by testing GSDMD-N, Caspase 1 , IL-18, and IL-1β in mice and HepG2 cells. Further exploring the mechanisms, we found that EA-induced pyroptosis depended on Cathepsin B (CTSB)-mediated NLRP3 inflammasome activation. Cell autophagy was closely related to lysosomes . Our study revealed that EA promoted hepatocyte autophagy, and activated autophagy induced lysosomal membrane permeabilization (LMP) and CTSB leakage . Inhibition of autophagy by 3-MA mitigated the CTSB leak, reduced the activation of the NLRP3 inflammasome, and then attenuated the EA-induced pyroptosis. In summary, these results indicated that EA induced hepatocyte pyroptosis via autophagy-CTSB-NLRP3 inflammasome pathway. The study revealed new insights into the toxicity mechanism of EA.
研究领域:
毒理学
·
细胞生物学
·
分子生物学
·
肝病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Biological Sciences
·
2026
·Vol. 22
·期 3
·1542
·
IF 10
Yini Li,Tongtong Tian,Qian Yu,Huiqin Jiang,Te Liu,Hao Wang,Ran Huo,Chenzheng Gu,Yu Liu,Ying Zhao,Chunyan Zhang,Yan Zhou,Jiyan Wang,Lin Ding,Chuyu Wang,Xinyi He,Wei Guo,Wenjing Yang,Beili Wang
Dietary intervention provides a novel approach for cancer therapy. Elaidic acid (EA), which accounts for 80-90% of total trans fatty acids in foods, has recently been found to exert anti-tumor effects. However, the biological functions and underlying mechanisms of EA remain elusive in hepatocellular carcinoma (HCC). In this study, targeted fatty acid metabolomics demonstrated that among 44 types of fatty acids, the concentration of EA decreased most significantly when comparing plasma from HCC patients with plasma from healthy people. Through in vivo assays using HCC orthotopic and xenograft mouse models, we further revealed that dietary EA attenuates HCC growth. Notably, when gut microbiota was depleted using a cocktail of antibiotics, the anti-tumor effect of EA was diminished, confirming that EA suppresses HCC tumor growth by modulating gut microbiota. Mechanistically, analysis of 16S ribosomal RNA sequencing showed that dietary EA markedly increases the abundance of intestinal Ligilactobacillus murinus (L. murinus) . Subsequent untargeted metabolomic sequencing analysis further demonstrated that dietary EA drives the production of L. murinus -derived spermidine (SPD), which attenuates HCC growth in vitro as well as in vivo . The observed impact correlated with the phosphorylation of p38 MAPK and the upregulation of biomarkers pertinent to apoptosis and proliferation, including tumor protein 53, bcl-2-associated X protein, and cysteine-requiring aspartate protease 3. Taken together, our findings highlight the important role of intestinal L. murinus -derived SPD in EA-mediated HCC suppression, thereby offering a promising dietary strategy for HCC treatment.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）