OGG1 mRNA expression and incision activity in rats are higher in foetal tissue than in adult liver tissue while 8-oxo-2′-deoxyguanosine levels are unchanged

DNA Repair ◽  
2002 ◽  
Vol 1 (9) ◽  
pp. 709-717 ◽  
Author(s):  
B Riis
2016 ◽  
Author(s):  
Oselyne TW Ong ◽  
Lauren J Young ◽  
Julie M Old

Background: Reference genes serve an important role as an endogenous control/standard for data normalisation in gene expression studies. Although reference genes have recently been suggested for marsupials, independent analysis of reference genes on different immune tissues is yet to be tested. Therefore, an assessment of reference genes is needed for the selection of stable, expressed genes across different marsupial tissues. Methods: The study was conducted on red-tailed phascogales (Phascogale calura) using five juvenile and five adult males. The stability of five reference genes (glyceraldehyde-3-phosphate dehydrogenase, GAPDH; β-Actin, ACTB; 18S rRNA, 18S; 28S rRNA, 28S; and ribosomal protein L13A, RPL13A) was investigated using SYBR Green and analysed with the geNorm application available in qBasePLUS software. Results: Gene stability for juvenile and adult tissue samples combined show that GAPDH was most stable in liver and lung tissue, and 18S in small intestine and spleen. While all reference genes were suitable for small intestine and spleen tissues, all reference genes except 28S were stable for lung and only 18S and 28S were stable for liver tissue. Separating the two age groups, we found that two different reference genes were considered stable in juveniles (ACTB and GAPDH) and adults (18S and 28S), and RPL13A was not stable for juvenile small intestine tissue. Except for 28S, all reference genes were stable in juvenile and adult lungs, and all five reference genes were stable in spleen tissue. Discussion: Based on expression stability, ACTB and GAPDH are suitable for all tissues when studying the expression of marsupials in two age groups, except for adult liver tissues. The expression stability between juvenile and adult liver tissue was most unstable, as the stable reference genes for juveniles and adults were different. Juvenile and adult lung, small intestine and spleen share similar stable reference genes, except for small intestine tissues where all reference genes were stable in adults but RPL13A was not suitable in juveniles.


Author(s):  
Takeshi Saito ◽  
Tomoro Hishiki ◽  
Keita Terui ◽  
Tetsuya Mitsunaga ◽  
Elena Terui ◽  
...  

2020 ◽  
Vol 79 (OCE2) ◽  
Author(s):  
Victor Sanchez ◽  
Anna Janina Engstler ◽  
Annette Brandt ◽  
Cheng Jun Jin ◽  
Dragana Rajcic ◽  
...  

AbstractBackground and Aims:General overnutrition, and a diet rich in fat and sugar are among the key risk factors for the development of metabolic diseases including diabetes type 2 and non-alcoholic fatty liver diseases (NAFLD). While being among the most commonly consumed oils world-wide, the effects of soybean oil on the development of metabolic diseases are yet not understood. Indeed, existing data is in part contradictory. Based on this background, the aim of the present study was to investigate the effects of soybean oil consumption on the development of non-alcoholic steatohepatitis (NASH), the more progressed stage of NAFLD, and insulin resistance.Methods:Female C57BL/6J mice were fed either a liquid standard control diet (C) or a liquid fat-, fructose- and cholesterol-rich diet (FFC, 25E% butterfat, 50% (wt/wt) fructose, 0.155% (wt/wt) cholesterol) or a FFC supplemented with soybean oil (FFC + S, 21E% butterfat + 4E% soy oil), with FFC and FFC + S-fed groups being pair fed for 13 weeks to induce steatohepatitis. After 7 and 12 weeks of feeding, a glucose tolerance test was performed. Indicators of liver damage, inflammation, intestinal barrier function and markers of insulin signaling cascade were measured in intestinal, liver and muscle tissue.Results:As expected FFC-fed mice developed early signs of NASH and insulin resistance. Despite similar caloric intake and body weight gain, development of NASH and insulin resistance were significantly attenuated in FFC + S-fed mice when compared to FFC-fed animals. Indeed, signs of hepatic inflammation e.g. number of inflammatory foci and neutrophils as well as activity of transaminase in plasma were almost at the level of control in FFC + S-fed mice. Prevalence of macrovesicular steatosis being the predominant type of fat accumulation found in FFC-fed animals was also markedly lower in FFC + S-fed mice. Furthermore, while in muscle and liver tissue of FFC-fed mice insulin receptors mRNA expression was significantly different from C-fed animals, insulin receptors expression in FFC + S-fed mice was almost at the level of controls. The protective effects of soybean oil supplementation on the development of metabolic alterations were associated with a protection against the induction of TLR4 mRNA expression and dependent signaling molecules in liver tissue.Conclusion:Taking together, our results indicate that supplementation with soybean oil may attenuate the development of diet-induced NASH and insulin resistance in mice and that this may be related to alteration of TLR4-dependent signaling cascade in liver tissue. (Funded in parts by UFOP e.V.)


2019 ◽  
Vol 104 (6) ◽  
pp. e60.1-e60
Author(s):  
BD van Groen ◽  
C Bi ◽  
R Gaedigk ◽  
V Staggs ◽  
D Tibboel ◽  
...  

BackgroundAlternative mRNA transcripts occur in >90% of human genes and may be triggered by developmental signals. The hepatic transporter OATP1B1 (gene name SLCO1B1) traffics substrates across the hepatic membrane, and shows age-related changes in protein expression. We aimed to predict novel isoforms of OATP1B1 by studying alternative splicing of SLCO1B1 in human paediatric post-mortem liver tissue, and the relationship of their mRNA expression with age.Methods mRNA expression of SLCO1B1 transcripts was determined using RNA sequencing (HISAT2/StringTie). Novel mRNA transcripts were considered of relevance when (1) the expression was >5% of the annotated isoform, (2) it was a SLCO1B7 and SCLO1B1 hybrid transcript, or (3) when the expression was associated with age. The software packages ORF-finder, TMpred and TOPO2 were used to predict the protein sequence and structure of the novel isoforms. Relationship of expression with age was studied with the Kruskal-Wallis test for age groups (fetal, 0–1.5 year, 1.5–6 year, 6–12 year and 12–18 year) and with Spearman correlation tests for age on continuous scale.ResultsIn 97 hepatic post-mortem tissues (gestational age median 16.4 [range 14.7–41.3] weeks, postnatal age 0.36 [0 - 17] years) 27 novel mRNA transcripts were detected. Of these, 13 were relevant: 2 isoforms are predicted to translate into amino acid sequences similar to the annotated isoform for OATP1B1, 9 isoforms may translate into truncated versions, and the expression of 8 isoforms was associated with age. None of the isoforms had an ORF that covered the SLCO1B7 region.ConclusionWe showed that novel SLCO1B1 mRNA isoforms potentially translate into OATP1B1 protein with unknown function, and that alternative splicing may well be a regulatory mechanism for SLCO1B1 expression during development. This data provides a better understanding of age-related changes in the expression of OATP1B1, and, with that, potentially improves prediction of disposition of endogenous and exogenous substrates.Disclosure(s)BG was supported, in part, by the Ter Meulen fund 2018 provided by the Royal Dutch Academy of Sciences. The National Institute of Child Health and Human Development Brain and Tissue Bank for Developmental Disorders at the University of Maryland is funded by the National Institutes of Health (NIH) contract HHSN275200900011C, reference number, N01-HD-9-0011 and the Liver Tissue Cell Distribution System is funded by NIH contract number N01-DK-7-0004/HHSN267200700004C.


2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Jakub Šuk ◽  
Jana Jašprová ◽  
David Biedermann ◽  
Lucie Petrásková ◽  
Kateřina Valentová ◽  
...  

Bilirubin is considered to be one of the most potent endogenous antioxidants in humans. Its serum concentrations are predominantly affected by the activity of hepatic bilirubin UDP-glucuronosyl transferase (UGT1A1). Our objective was to analyze the potential bilirubin-modulating effects of natural polyphenols from milk thistle (Silybum marianum), a hepatoprotective herb. Human hepatoblastoma HepG2 cells were exposed to major polyphenolic compounds isolated from milk thistle. Based on in vitro studies, 2,3-dehydrosilybins A and B were selected as the most efficient compounds and applied either intraperitoneally or orally for seven days to C57BL/6 mice. After, UGT1A1 mRNA expression, serum, intrahepatic bilirubin concentrations, and lipoperoxidation in the liver tissue were analyzed. All natural polyphenols used increased intracellular concentration of bilirubin in HepG2 cells to a similar extent as atazanavir, a known bilirubinemia-enhancing agent. Intraperitoneal application of 2,3-dehydrosilybins A and B (the most efficient flavonoids from in vitro studies) to mice (50 mg/kg) led to a significant downregulation of UGT1A1 mRNA expression (46±3% of controls, p<0.005) in the liver and also to a significant increase of the intracellular bilirubin concentration (0.98±0.03vs.1.21±0.02 nmol/mg, p<0.05). Simultaneously, a significant decrease of lipoperoxidation (61±2% of controls, p<0.005) was detected in the liver tissue of treated animals, and similar results were also observed after oral treatment. Importantly, both application routes also led to a significant elevation of serum bilirubin concentrations (125±3% and 160±22% of the controls after intraperitoneal and oral administration, respectively, p<0.005 in both cases). In conclusion, polyphenolic compounds contained in silymarin, in particular 2,3-dehydrosilybins A and B, affect hepatic and serum bilirubin concentrations, as well as lipoperoxidation in the liver. This phenomenon might contribute to the hepatoprotective effects of silymarin.


ACS Omega ◽  
2020 ◽  
Vol 5 (10) ◽  
pp. 4816-4827
Author(s):  
Nidal Ghosheh ◽  
Barbara Küppers-Munther ◽  
Annika Asplund ◽  
Christian X. Andersson ◽  
Petter Björquist ◽  
...  

2008 ◽  
Vol 366 (2) ◽  
pp. 367-372 ◽  
Author(s):  
Natasha Wright ◽  
Lisa Samuelson ◽  
Maggie H. Walkup ◽  
Prakash Chandrasekaran ◽  
David A. Gerber

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