15-Deoxy-Δ^12,14-prostaglandin J2 (15d-PGJ2) plays an important role in cell proliferation and apoptosis with various inhibitory effects. We investigated whether 15d-PGJ2 influence proliferation and apoptosis of human microvascular endothelial cells (HMEC-1), and suppression of the nuclear factor (NF)-κB activity and PI3K/AKT/mTOR signal pathway. Cell proliferation was analyzed using the MTS/PMS and colony formation assays. We analyzed the cell cycle using flow cytometry, while quantitative polymerase chain reaction (qPCR) measured mRNA expression, and immunoblot analysis quantified protein expression. 15d-PGJ2 inhibited cell growth and colony formation. In addition, it reduced the expression of cyclin-dependent kinase 4 and 6 (CDK4/6) and cyclin D1 mRNA but increased p21 mRNA expression. Apoptosis was increased during cell cycle progression and induced, as evident from the expression of apoptosis-related proteins, such as reduced Bcl-2 expression and increased Bax, caspase-3, and caspase-9 expression. Furthermore, the phosphorylation of NF-κB and PI3K/AKT/mTOR proteins was suppressed. This study found that 15d-PGJ2 inhibits cell proliferation, induces apoptosis, and regulates cell cycle- and apoptosis-related gene expression by suppressing the NF-κB and PI3K/AKT/mTOR pathways in HMEC-1 cells.

2025-08-01·FOOD CHEMISTRY

Metabolomics unravels the formation pathway of advanced glycation end products in preserved egg yolk mediated by OH− during pickling

Article

作者: Xiang, Xiaole ; Dong, Shiqin ; Li, Shugang ; Huang, Yiqun ; Ye, Lin ; Yu, Zhuosi ; Chen, Le ; He, Yu

Metabolomics was first applied to explore the formation pathway and regulatory factors for advanced glycation end products (AGEs) in preserved egg yolk (PEY) during pickling. Most reactions that contributed to formation of AGEs, including oxidation and/or degradation of matrix/precursors and Maillard reaction, occurred primarily in PEY in early stage, and lipid oxidation occurred prior to protein oxidation. Additionally, the formation of N^ε-carboxymethyl-lysine (CML) in PEY was mainly attributed to glyoxal derived from D-glucuronic acid in early stage based on the correlation between metabolites and AGEs. Reactive oxygen radicals from oxidized lipids also promoted the enrichment of CML and N^ε-carboxymethyl-lysine (CEL). Moreover, during later stage, the accumulation of CEL was enhanced through methylglyoxal from Schiff bases, and acidic compounds could inhibit AGEs via hindering Maillard reaction. This manuscript pioneered the application of metabolomics to reveal the formation pathway of AGEs, and will provide new perspective on AGEs formation in foods.

2025-07-08·CIRCULATION

Intracellular L-PGDS–Derived 15d-PGJ2 Inhibits CaMKII Through Lipoxidation to Alleviate Cardiac Ischemia/Reperfusion Injury

Article

作者: Liu, Yitong ; Luo, Xile ; Li, Jiayi ; Hu, Xinli ; Zhu, Wenneng ; Xie, Peng ; Shang, Haibao ; Zhang, Shuyang ; Chen, Zhixing ; Hu, Peiyu ; Jin, Li ; Xiao, Rui-Ping ; Jiao, Zishan ; Zhang, Junxia ; Li, Fan ; Zhang, Yan ; Wang, Zeyuan ; Hu, Qingmei ; Zheng, Wen ; Duanmu, Jiaxin

BACKGROUND::

Myocardial ischemia/reperfusion (I/R) injury is a substantial challenge to the management of ischemic heart disease, the leading cause of mortality worldwide. Arachidonic acid (AA) is a prominent polyunsaturated fatty acid in the human body and plays an important role in various physiological and pathological conditions. AA metabolic enzymes determine AA levels; however, currently there is no comprehensive analysis of AA enzymes in cardiac I/R injury.

METHODS::

The profiling of AA metabolic enzymes was analyzed with the RNA sequencing transcriptome data from the mouse heart tissues with I/R injury. Cultured neonatal and adult rat ventricular myocytes, human embryonic stem cell–derived cardiomyocytes, and in vivo mouse I/R models were used to confirm the role of L-PGDS (lipocalin-type prostaglandin D2 synthase)/15d-PGJ2 in I/R injury. A biotin-tagged 15d-PGJ2 analog combined with liquid chromatography–tandem mass spectrometry was used to identify the downstream signaling of L-PGDS/15d-PGJ2.

RESULTS::

Based on the transcriptome data and experimental validations, L-PGDS, together with its downstream metabolite 15d-PGJ2, was downregulated in cardiac tissue with I/R injury. Functionally, L-PGDS overexpression mitigates myocardial I/R injury, whereas knockdown exacerbates the damage. Supplementation of 15d-PGJ2 alleviated I/R injury. Mechanistically, 15d-PGJ2 covalently bound to the CaMKII (Ca 2+ /calmodulin dependent protein kinase II) and induced lipoxidation of its cysteine 495 (CaMKII-δ9) to dampen the formation of CaMKII oligomers and alleviate its overactivation, consequently ameliorating cardiomyocyte death and cardiac injury.

CONCLUSIONS::

Our study uncovered L-PGDS/15d-PGJ2/CaMKII signaling as a new mechanism underlying I/R-induced cardiomyocyte death. This provides new mechanistic insights and therapeutic targets for myocardial I/R injury and subsequent heart failure. We also showed that lipoxidation is a new post-translational modification type for CaMKII, deepening our understanding of the regulation of its activity.

100 项与 15d-PGJ2 相关的药物交易

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