未定位的代谢学和转录学研究显示,在重复性自发性流产中,活性化铁灭的代谢谱
Xiaoqing Wu1, Shuqiong He2, Jinzhou Lu3
1Medical Genetic Diagnosis and Therapy Center, Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian, China; Fujian Provincial Key Laboratory for Prenatal Diagnosis and Birth Defect, Fuzhou, Fujian, China; Department of Laboratory Medicine, Fujian Medical University, Fuzhou, Fujian, China; Key Laboratory of Clinical Laboratory Technology for Precision Medicine (Fujian Medical University), Fuzhou, Fujian, China.
铁,一种依赖于铁的细胞死亡,与反复性自发性流产 (RSA) 有关. 这项研究揭示了RSA小组织中与ferroptosis相关的明显的代谢和基因表达特征,提供了新的诊断和治疗途径.
科学领域:
- 产科 产科 产科 产科 产科
- 细胞生物学 细胞生物学
- 代谢学 代谢学 代谢学
- 基因组学就是基因组学.
背景情况:
- 复发性自发性流产 (RSA) 是一个重要的产科挑战,其分子基础不明.
- 铁,一种由铁的积累和脂质过氧化驱动的受调细胞死亡的形式,在各种病理中越来越被认可.
研究的目的:
- 为了研究铁化在重复性自发性流产的分子机制中的作用.
- 为了识别与RSA小组织中的铁化相关的明显的代谢和转录基因特征.
主要方法:
- 非向的UPLC-MS/MS代谢分析来自RSA患者和对照者的小组织.
- 正角部分最小平方差分分析 (OPLS-DA) 和随机森林分析用于代谢分析.
- 用于转录组分析的RNA测序 (RNA-seq),包括基因组丰富分析 (GSEA),基因本体学 (GO) 和基因和基因组 (KEGG) 京都百科全书的途径分析.
- 反转录聚合酶链反应 (RT-PCR) 验证关键基因表达变化.
主要成果:
- 在RSA小组织中发现了由铁灭表型特征的明显的代谢特征,包括升高的脂质过氧化和降低的氨酸,血清素,氨酸,谷氨酸和谷氨酸的水平.
- 代谢分析强调了谷氨酸代谢,氨酸,氨酸,SAM和牛代谢,聚胺代谢和脂质过氧化代谢途径的变化.
- RNA-seq揭示了89个与ferroptosis相关的基因的改变表达,并显著丰富了ferroptosis通路.
- 验证证实RSA小组织中ACSL4,FTH1,TFRC,PTGS2的mRNA表达升高,GPX4和SLC7A11的表达降低.
结论:
- 铁死在重复性自发性流产的病原发生中起着关键作用.
- 鉴定的代谢和转录基因变化为RSA诊断提供了潜在的生物标志物.
- 这些发现表明,针对RSA的管理,针对ferroptosis的新型治疗策略.
更多相关视频
03:39Author Spotlight: Multi-Layered Approach to Understand Postnatal Functions of Pancreatic Islets in Non-Human Primates
Published on: November 8, 2024
11:02Identification and Quantification of Deranged Metabolites in Critically Ill Patients Using NMR-Based Metabolomics
Published on: November 29, 2024
相关概念视频
Non-LTR Retrotransposons
Translation
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of Life
Phase II Reactions: Miscellaneous Conjugation Reactions
A key example involves the conjugation of cyanide ions, which impair cellular respiration and alter hemoglobin into non-oxygen-carrying cyanmethemoglobin. To neutralize this threat, a sulfur atom from thiosulphate is transferred to the cyanide ion, catalyzed by the enzyme rhodanese, resulting in an inactive compound called thiocyanate. The production of...
Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase
Drug toxicity: Idiosyncratic Reactions
Bioactivation and Tissue Toxicity
