Project description:We reported the hepatic gene expression profiling in male Sprague-Dawley rats treated by different concentrations of perfluorooctanoic acid (PFOA) for 7, 14, and 28 days. We confirmed that PFOA induced liver tumor formation was mainly through the activation of peroxisome proliferator-activated receptor α (PPARα). We identified a panel of 7 genes (Cyp4a1, Nr1d1, Acot2, Vnn, Ehhadh, and Acot1) that might serve as the biomarkers for PPARα activation. We also meausred the apical endpoints of PPARα activation and found a good correlation with the expression level of these biomarker genes. Consitituitive androstane receptor mediated Cyp2b enzymatic activity and gene expression was also upregulated by PFOA in a dose-response manner. On the other hand, acyl hydrocarbon receptor (AhR) target gene Cyp1a2 were significantly downregulated at all time points studied. To our surprise, results of KEGG and Reactome pathway analyses suggested that PFOA did not drive the cell cycles and proliferations in the liver. While some of the DNA replication genes such as Pold2 and Mcm8 were upregulated by PFOA treatment, several key cyclin-dependent cell growth genes, including Ccnd1, Ccne2, Ccnb1, and Ccna2 were all significantly downregulated by PFOA in a dose-dependent manner, especailly at 28 days. Ingenuity Pathway Analysis also indicated that PFOA led to a suppression of liver cancer related pathways at later time points studied. These results suggest that while PFOA clearly induced PPARα activation, the increased cell growth (the second key event in the tumor mode of action), was transient and tightly regulated by feedback mechanisms. Whether such changes will eventually cause the formation of preneoplastic foci and liver tumors in rats remains unclear.
Project description:The biological effects of the pesticide and complex I inhibitor tebufenpyrad (TEBU) on liver cells were investigated by proteomic approaches. Cellular contents and culture media were analyzed in dose-response experiments on primary rat hepatocytes (PRHs).
Project description:We have reported that mRNAs are present in bovine milk. But, it is unknown the roles of milk mRNAs. To clarify the roles of milk mRNAs, experimental animal such as rat study would be needed. However, it is unclear whether rat milk also contains mRNAs. Thus, we have employed microarray to show that rat milk also contains mRNAs.
Project description:We have reported that microRNAs are present in human and bovine milk. But, it is unknown the roles of milk miRNAs. To clarify the roles of milk miRNAs, experimental animal such as rat study would be needed. However, it is unclear whether rat milk also contains miRNAs. Thus, we have employed microarray to show that rat milk also contains miRNAs.
Project description:this paper used Mass spectrometry, Fast-seq, and catTFRE to study the pattern of 6316 proteins as well as 387 Transcription factors associated with PM2.5 in both short-term and long-term rat injury models.
Project description:The study was performed using primary rat hepatocyte in culture from 4 adult male Sprague-Dawley rats to investigate the changes in gene expression under low dose (4μM) and short exposure (3hrs) of cadmium chloride. By comparing the gene expression profiles of control and cadmium-treated cells, the most dramatic and significant changes were for those genes associated with transcriptional regulation, antioxidant response and control of protein integrity. Changes in other genes involved in cellular physiological responses such as inflammation, growth and apoptosis were also observed. Results were further confirmed by quantitative real time polymerase chain reaction (qRT-PCR). Keywords: early protective responses
Project description:MicroRNAs (miRNAs) are small non-coding RNAs that function as regulators of gene expression to control cell growth and differentiation. MiRNA levels are substantially altered in various types of tumors and have been used as biomarkers in defining malignant status. However, studies on responses of miRNA expression to carcinogen insults in their target tissues are rare. In this study, we analyzed miRNA expression in the livers of rats treated with carcinogenic dose of comfrey (Symphytum officinale), a rat botanical carcinogen.
Project description:The present study focuses on the identification of the gene expression profile of neonatal rat cardiomyocytes (NRVCMs) after dynamic mechanical stretch through microarrays of RNA isolated from cells stretched for 2, 6 or 24 h.
Project description:Triethylene glycol dimethacrylate (TEGDMA) is commonly used in polymer resin-based dental materials. This projected investigated molecular mechanisms of TEGDMA toxicity by identifying time- and dose dependent effects on the proteome of human THP-1 monocytes. Effects of different concentrations (0.07mM-5mM) and exposure times (0-72h) of TEGDMA on cell viability, proliferation, and morphology were determined by a real-time viability assay, automated cell counting, and electron microscopy, and laid the fundament for choice of exposure scenarios in the proteomic experiments. Cells were metabolically labelled (SILAC), and exposed to 0.3mM or 2.5mM TEGDMA for 6h or 16h prior to LC-MS/MS analyses. Regulated proteins were analysed with the STRING database. Cells exposed to 0.3mM TEGDMA showed increased viability, and time-dependent upregulation of proteins associated with stress/oxidative stress, autophagy, and cytoprotective functions. Cells exposed to 2.5mM TEGDMA showed diminished viability, and a protein expression profile associated with oxidative stress, DNA-damage, mitochondrial dysfunction and cell-cycle inhibition. Altered expression of immune genes was observed in both groups.