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CELLULAR & MOLECULAR BIOLOGY LETTERS · 2022 ·Vol. 27 ·期 1 ·1-13 · IF 8.702

Slc25a5 regulates adipogenesis by modulating ERK signaling in OP9 cells

Zhu Shenglong,Wang Wei,Zhang Jingwei,Ji Siyu,Jing Zhe,Chen Yong Q.

Background A comprehensive understanding of the molecular mechanisms of adipogenesis is a critically important strategy for identifying new targets for obesity intervention. Methods Transcriptomic and lipidomic approaches were used to explore the functional genes regulating adipogenic differentiation and their potential mechanism of action in OP9 cells and adipose-derived stem cells. Oil Red O staining was used to detect oil droplets in adipocytes. Results RNA sequencing (RNA-seq) showed that Slc25a5 expression was significantly upregulated in adipogenic differentiation. Depletion of Slc25a5 led to the suppressed expression of adipogenesis-related genes, reduced the accumulation of triglycerides, and inhibited PPARγ protein expression. Moreover, the knockdown of Slc25a5 resulted in significant reduction of oxidative phosphorylation (OXPHOS) protein expression (ATP5A1, CQCRC2, and MTCO1) and ATP production. The RNA-seq and real-time quantitative polymerase chain reaction (RT–qPCR) results suggested that adipogenic differentiation is possibly mediated by ERK1/2 phosphorylation, and this hypothesis was confirmed by intervention with PD98059 (an ERK 1/2 inhibitor). Conclusions This study indicates that Slc25a5 inhibits adipogenesis and might be a new therapeutic target for the treatment of obesity.

CAS / MDL: 28822-58-4
研究领域: 分子生物学 · 细胞生物学 · 肥胖研究
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Bioactive Materials · 2024 · IF 18

Novel ultrathin ferrous sulfide nanosheets: Towards replacing black phosphorus in anticancer nanotheranostics

Yuan Gao,Mengyao Mu,Yiju Wei,Bowen Yan,Hui Liu,Kai Guo,Mengmeng Zhang,Xiaohui Dai,Xiao Sun,David Tai Leong

Biodegradable two-dimensional nanomaterials could be a significant breakthrough in the field of oncology nanotheranostic agents, which are rapidly emerging as promising candidates for tumor theranostic applications. Herein, a novel biodegradable ferrous sulfide nanosheet (FeS NS) is developed. Compared to the traditional photothermal material, black phosphorus nanosheet (BP NS), FeS demonstrates superior degradability and enhanced photothermal performance, and making it ideal for efficient photothermal therapy (PTT) of tumors. In the acidic tumor microenvironment, FeS degrades and releases H 2 S, which inhibits mitochondrial respiration and ATP production. This process leads to a reduction in heat shock protein expression, lowering the resistance of tumor cells to photothermal stimulation, and improving the efficacy of PTT. The released Fe 2+ exhibits efficient peroxidase activity, triggering ferroptosis in tumor cells. Furthermore, due to its superparamagnetic nature, FeS NSs could accumulate at the tumor site and provide a strong magnetic resonance imaging (MRI) signal for imaging-guided tumor therapy. Overall, as a promising alternative to BP, the FeS NSs are a potentially innovative nanotheranostic agent of tumors, offering a synergistic approach to ferroptosis−PTT with MRI guidance.

研究领域: 纳米技术 · 肿瘤学 · 诊疗一体化 · 材料科学
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INDUSTRIAL CROPS AND PRODUCTS · 2021 · IF 5.645

Integrative omic analysis reveals the improvement of alkaloid accumulation by ultraviolet-B radiation and its upstream regulation in Catharanthus roseus

Zhuoheng Zhong,Shengzhi Liu,Songling Han,Yaohan Li,Minglei Tao,Amin Liu,Qiang He,Sixue Chen,Criag Dufresne,Wei Zhu,Jingkui Tian

Indole alkaloids from Catharanthus roseus (L.) G. Don were valued for their wide spectrum of pharmaceutical effects. Their biosynthesis is modulated by various abiotic factors including ultraviolet B radiation which induced ATP production and led to accumulation of indole alkaloids. To investigate the regulatory mechanism of secondary metabolism in the leaf mitochondria of C. roseus under ultraviolet B radiation, combinatory study of proteomic and metabolomic analyses of C. roseus was performed. ATP export in the leaves of C. roseus increased under UVB radiation, which required mitochondrial ATP synthase. Proteins related to mitochondrial complexes II/IV and their gene expression levels increased, and those related to mitochondrial complex I decreased. Proteins related to the methylerythritol phosphate pathway, especially geranylgeranyl pyrophosphate synthase, increased under ultraviolet B radiation. Metabolites whose levels changed were mainly alkaloids, organic acids, carbohydrates, phenylpropanoids, and fatty acids, while eight indole alkaloids increased. Integrative analysis of omics data indicated that the metabolism of glutamate and tyrosine was downregulated. These results suggest that ultraviolet B radiation induces dynamic changes in mitochondria in C. roseus , which guarantees ATP production, regulates the flux of the methylerythritol phosphate pathway to the biosynthesis of monoterpene moieties, and leads to accumulation of various indole alkaloids.

研究领域: 植物生物化学 · 分子生物学 · 药理学 · 环境科学
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