1.Momordicine I alleviates isoproterenol-induced cardiomyocyte hypertrophy through suppression of PLA2G6 and DGK-ζ
Hongming LI ; Yumei QIU ; Mengdie XIE ; Changsheng OUYANG ; Xiaoyun DING ; Hao ZHANG ; Wei DONG ; Yinhua XIONG ; Xilan TANG
The Korean Journal of Physiology and Pharmacology 2023;27(1):75-84
This study aimed to observe the protective effect of momordicine I, a triterpenoid compound extracted from momordica charantia L., on isoproterenol (ISO)-induced hypertrophy in rat H9c2 cardiomyocytes and investigate its potential mechanism. Treatment with 10 μM ISO induced cardiomyocyte hypertrophy as evidenced by increased cell surface area and protein content as well as pronounced upregulation of fetal genes including atrial natriuretic peptide, β-myosin heavy chain, and α-skeletal actin; however, those responses were markedly attenuated by treatment with 12.5 μg/ml momordicine I. Transcriptome experiment results showed that there were 381 and 447 differentially expressed genes expressed in comparisons of model/control and momordicine I intervention/model, respectively. GO enrichment analysis suggested that the anti-cardiomyocyte hypertrophic effect of momordicine I may be mainly associated with the regulation of metabolic processes. Based on our transcriptome experiment results as well as literature reports, we selected glycerophospholipid metabolizing enzymes group VI phospholipase A 2 (PLA2G6) and diacylglycerol kinase ζ (DGK-ζ) as targets to further explore the potential mechanism through which momordicine I inhibited ISO-induced cardiomyocyte hypertrophy.Our results demonstrated that momordicine I inhibited ISO-induced upregulations of mRNA levels and protein expressions of PLA2G6 and DGK-ζ. Collectively, momordicine I alleviated ISO-induced cardiomyocyte hypertrophy, which may be related to its inhibition of the expression of glycerophospholipid metabolizing enzymes PLA2G6 and DGK-ζ.
2.Metabolic profiles of serum lysophosphatidylcholine and amino acids in rats with nonalcoholic fatty liver disease
Meiyu ZHAO ; Xinyue SHI ; Shuling ZHOU ; Haijun LI ; Shuting FAN ; Yinhua XIONG
Acta Laboratorium Animalis Scientia Sinica 2024;32(4):477-484
Objective To use metabolomics method to study the metabolic profiles of amino acids and lysophosphatidylcholine(LPC)in the serum of rats with nonalcoholic fatty liver disease(NAFLD),to identify biomarkers for NAFLD,and to speculate on the possible mechanism responsible for its occurrence.Methods NAFLD rats were prepared by feeding a high-fat diet and intraperitoneal injection of carbon tetrachloride.Levels of 15 LPCs and 18 amino acids in the serum were determined in control and NAFLD rats by liquid chromatography-mass spectrometry.Changes in serum LPC and amino acid metabolic profiles in NAFLD rats were analyzed by principal component analysis and orthogonal partial least squares discriminant analysis.Correlations between biomarkers and NAFLD were analyzed by Pearson's correlation analysis.Results The metabolic profiles of serum LPC and amino acids differed significantly between the NAFLD group and the control group and were completely distinct.LPC(20∶1),arginine,and glutamic acid had significant contributions to NAFLD and were identified as biomarkers.Furthermore,LPC(20∶1)and arginine were significantly correlated with serum biochemical indicators such as aspartate transaminase,alanine transaminase,low-density lipoprotein,and total bilirubin.Conclusions The metabolic profiles of serum LPC and amino acids may be closely related to NALFD.