Biochemical disorders associated with antiproliferative effect of dehydroepiandrosterone in hepatoma cells as revealed by LC-based metabolomics

Cheng, Mei‐Ling; Shiao, Ming‐Shi; Chiu, Daniel T.; Weng, Shiue-Fen; Tang, Hsiang-Yu; Ho, Hung‐Yao

doi:10.1016/j.bcp.2011.07.104

Cited by 23 publications

(16 citation statements)

References 81 publications

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“…In the tissue acylcarnitine profiles, the most significant features were the overall decreases in short‐ and medium‐chain acylcarnitines and the increases in saturated long‐chain acylcarnitines in HCC tissues compared with ANTs. Although similar tendencies have been uncovered in several HCC‐related metabolomics studies performed at both the serum and tissue levels, the relevant mechanism responsible for this effect has rarely been investigated. Noland et al performed comprehensive metabolic profiling on rats given high‐fat diets to investigate the influence of carnitine insufficiency caused by aging and overnutrition on mitochondrial function.…”

Section: Discussionmentioning

confidence: 88%

Metabolic profiling analysis upon acylcarnitines in tissues of hepatocellular carcinoma revealed the inhibited carnitine shuttle system caused by the downregulated carnitine palmitoyltransferase 2

Zhang

et al. 2019

Molecular Carcinogenesis

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The carnitine shuttle system (CSS) plays a crucial role in the transportation of fatty acyls during fatty acid β‐oxidation for energy supplementation, especially in cases of high energy demand, such as in cancer. In this study, to systematically characterize alterations of the CSS in hepatocellular carcinoma (HCC), acylcarnitine metabolic profiling was carried out on 80 pairs of HCC tissues and adjacent noncancerous tissues (ANTs) by using ultra‐performance liquid chromatography coupled to mass spectrometry. Twenty‐four acylcarnitines classified into five categories were identified and characterized between HCCs and ANTs. Notably, increased saturated long‐chain acylcarnitines (LCACs) and decreased short‐ and medium‐chain acylcarnitines (S/MCACs) were simultaneously observed in HCC samples. Subsequent correlation network and heatmap analysis indicated low correlations between LCACs and S/MCACs. The mRNA and protein expressions of carnitine palmitoyltransferase 2 (CPT2) was significantly downregulated in HCC samples, whereas CPT1A expression was not significantly changed. Correspondingly, the relative levels of S/MCACs were reduced and those of LCACs were increased in BEL‐7402/CPT2‐knockdown cells compared to negative controls. Both results suggested that decreased shuttling efficiency in HCC might be associated with downregulation of CPT2. In addition, decreases in the mRNA expression of acetyl‐CoA acyltransferase 2 were also observed in HCC tissues and BEL‐7402/CPT2‐knockdown cells, suggesting potential low β‐oxidation efficiency, which was consistent with the increased expression of stearoyl‐CoA desaturase 1 in both samples. The systematic strategy applied in our study illustrated decreased shuttling efficiency of the carnitine shuttle system in HCC and can provide biologists with an in‐depth understanding of β‐oxidation in HCC.

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Section: Discussionmentioning

confidence: 88%

Metabolic profiling analysis upon acylcarnitines in tissues of hepatocellular carcinoma revealed the inhibited carnitine shuttle system caused by the downregulated carnitine palmitoyltransferase 2

Zhang

et al. 2019

Molecular Carcinogenesis

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“…The erythrocyte membrane was incubated with 7KCh or cholesterol at 37 °C for 4 h, after which the membrane-bound 7KCh or cholesterol in the ghost pellet was diluted to the indicated concentrations for a viability test. Cell viability was determined by a neutral red assay, as previously described [23] .…”

Section: Methodsmentioning

confidence: 99%

Lipidomics reveals accumulation of the oxidized cholesterol in erythrocytes of heart failure patients

Tang

Wang

et al. 2018

Redox Biology

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Lipids play an important role in the pathogenesis of cardiovascular disease. Changes in lipids of erythrocytes are indicative of the outcome of pathophysiological processes. In the present study, we assessed whether the lipid profiles of erythrocytes from heart failure (HF) patients are informative of their disease risk. The lipidomes of erythrocytes from 10 control subjects and 29 patients at different HF stages were analyzed using liquid chromatography time-of-flight mass spectrometry. The lipid composition of erythrocytes obtained from HF patients was significantly different from that of normal controls. The levels of phosphatidylcholines (PCs), phosphatidylethanolamines (PEs), and sphingomyelins decreased in HF erythrocytes as compared with those of control subjects; however, the levels of lysoPCs, lysoPEs, and ceramides increased in HF erythrocytes. Notably, the oxidized cholesterol 7-ketocholesterol (7KCh) accumulated to higher level in HF erythrocytes than in plasma from the same patients. We further validated our findings with a cohort of 115 subjects of control subjects (n=28) and patients (n=87). Mechanistically, 7KCh promoted reactive oxygen species (ROS) formation in cardiomyocytes; and induced their death, probably through an ATF4-dependent pathway. Our findings suggest that erythrocytic 7KCh can be a risk factor for HF, and is probably implicated in its pathophysiology.

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“…The supernatant was dried under nitrogen gas, and dissolved in 400 ll of H 2 O containing 0.1% formic acid for LC-TOF-MS analysis. The procedure was carried out by the method of Cheng et al (15). The details are provided in the Supplementary Data.…”

Section: Global Metabolite Analysesmentioning

confidence: 99%

Inability to Maintain GSH Pool in G6PD-Deficient Red Cells Causes Futile AMPK Activation and Irreversible Metabolic Disturbance

Tang

Ho²,

Wu³

et al. 2015

Antioxidants & Redox Signaling

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Normal and G6PD-deficient RBCs differ in their responses to oxidants. Normal cells have adequate NADPH regeneration for maintenance of GSH pool. In contrast, G6PD-deficient cells are unable to regenerate enough NADPH under a stressful situation, and switch to biosynthetic pathway for GSH supply. Rapid GSH exhaustion causes energy crisis and futile AMPK activation. Our findings suggest that drug-induced oxidative stress differentially affects metabolism and metabolite signaling in normal and G6PD-deficient cells. It also provides an insight into the pathophysiology of acute hemolytic anemia in G6PD-deficient patients.

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Biochemical disorders associated with antiproliferative effect of dehydroepiandrosterone in hepatoma cells as revealed by LC-based metabolomics

Cited by 23 publications

References 81 publications

Metabolic profiling analysis upon acylcarnitines in tissues of hepatocellular carcinoma revealed the inhibited carnitine shuttle system caused by the downregulated carnitine palmitoyltransferase 2

Metabolic profiling analysis upon acylcarnitines in tissues of hepatocellular carcinoma revealed the inhibited carnitine shuttle system caused by the downregulated carnitine palmitoyltransferase 2

Lipidomics reveals accumulation of the oxidized cholesterol in erythrocytes of heart failure patients

Inability to Maintain GSH Pool in G6PD-Deficient Red Cells Causes Futile AMPK Activation and Irreversible Metabolic Disturbance

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