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Effects of glucose exposures on gene expressions in HepG2 cells

ABSTRACT: SULT1E1, the enzyme that specifically and effectively sulfates estrogens to its inactive forms-sulfated estrogens has been found to be highly induced in high glucose (450 mg/dL) cultured human liver hepatocellular carcinoma HepG2 cells. To confirm the SULT1E1 transcription in response to glucose exposures and to investigate whether glucose signal may alter the other xenobiotic metabolizing enzyme transcripts in HepG2 cells, we have conducted whole genome microarray expression profiling as a platform to identify genes that may response to glucose exposures. HepG2 cells were exposed to low glucose (40 mg/dL) or high glucose (450 mg/dL) DMEM for 48 hours respectively. The xenobiotic metabolic enzyme transcripts such as SULTs, CYPs, UGTs and GSTs were significantly altered in response to glucose exposures.

ORGANISM(S): Homo sapiens

PROVIDER: GSE140867 | GEO | 2020/08/26

REPOSITORIES: GEO

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Project description:Background: Pre-existing metabolic diseases may predispose individuals to particulate matter (PM)-induced adverse health effects. However, the differences in susceptibility of various metabolic diseases to PM-induced lung injury and their underlying mechanisms have yet to be fully elucidated. Results: Type 1 diabetes (T1D) or diet-induced obesity (DIO) murine models were generated by injection of streptozotocin or feeding a 45% high-fat diet for 10 weeks, respectively, and subjected to 4-week real-ambient PM exposure in Shijiazhuang, China (mean PM2.5 concentration 95.77 μg/m3). Pulmonary and systemic injury was assessed, and the underlying mechanisms were explored through transcriptomics analysis. Compared with normal diet (ND)-fed mice, T1D mice exhibited severe hyperglycemia with a blood glucose of 350 mg/dL, while DIO mice displayed moderate obesity and marked dyslipidemia with a slightly elevated blood glucose of 180 mg/dL. T1D and DIO mice were susceptible to PM-induced lung injury, manifested by inflammatory changes such as interstitial neutrophil infiltration and alveolar septal thickening. Notably, the acute lung injury scores were higher by 79.57% and 48.47%, respectively, than that of ND-fed mice. Lung transcriptome analysis revealed that increased susceptibility to PM exposure was associated with perturbations in multiple pathways including glucose and lipid metabolism, inflammatory responses, oxidative stress, cellular senescence, and tissue remodeling. Functional experiments confirmed that changes in biomarkers of macrophage (F4/80), lipid peroxidation (4-HNE), cellular senescence (SA-β-gal), and airway repair (CCSP) were most pronounced in the lungs of PM-exposed T1D mice. Furthermore, pathways associated with xenobiotic metabolism showed metabolic state- and tissue-specific perturbation patterns. Upon PM exposure, activation of nuclear receptor (NR) pathways and inhibition of the glutathione (GSH)-mediated detoxification pathway were evident in the lungs of T1D mice, and a significant upregulation of NR pathways was present in the livers of T1D mice. Conclusions: These differences might contribute to differential susceptibility to PM exposure between T1D and DIO mice. These findings provide new insights into the health risk assessment of PM exposure in populations with metabolic diseases.