scholarly journals The role of organic anion transporting polypeptides (OATPs/SLCOs) in the toxicity of different microcystin congeners in vitro: A comparison of primary human hepatocytes and OATP-transfected HEK293 cells

2010 ◽  
Vol 245 (1) ◽  
pp. 9-20 ◽  
Author(s):  
A. Fischer ◽  
S.J. Hoeger ◽  
K. Stemmer ◽  
D.J. Feurstein ◽  
D. Knobeloch ◽  
...  
Keyword(s):  
Organic Anion ◽  
Human Hepatocytes ◽  
Hek293 Cells ◽  
Organic Anion Transporting Polypeptides ◽  
Primary Human Hepatocytes

Effects of anthocyans on the expression of organic anion transporting polypeptides (SLCOs/OATPs) in primary human hepatocytes

2015 ◽  
Vol 6 (3) ◽  
pp. 772-779 ◽  
Author(s):  
Juliane Riha ◽  
Stefan Brenner ◽  
Alzbeta Srovnalova ◽  
Lukas Klameth ◽  
Zdenek Dvorak ◽  
...  
Keyword(s):  
Organic Anion ◽  
Human Hepatocytes ◽  
Organic Anion Transporting Polypeptides ◽  
Primary Human Hepatocytes ◽  
Naturally Occurring

Anthocyans (anthocyanins and their aglycones anthocyanidins) are colorful pigments, naturally occurring in fruits. Their influence on the expression of “liver-specific”SLCOs/OATPs was studied.

scholarly journals Implications of Efficient Hepatic Delivery by Tenofovir Alafenamide (GS-7340) for Hepatitis B Virus Therapy

2015 ◽  
Vol 59 (6) ◽  
pp. 3563-3569 ◽  
Author(s):  
Eisuke Murakami ◽  
Ting Wang ◽  
Yeojin Park ◽  
Jia Hao ◽  
Eve-Irene Lepist ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Human Hepatocytes ◽  
Target Tissue ◽  
Small Contribution ◽  
Primary Human Hepatocytes ◽  
B Virus ◽  
Tenofovir Alafenamide ◽  
Pharmacologically Active

ABSTRACTTenofovir alafenamide (TAF) is a prodrug of tenofovir (TFV) currently in clinical evaluation for treatment for HIV and hepatitis B virus (HBV) infections. Since the target tissue for HBV is the liver, the hepatic delivery and metabolism of TAF in primary human hepatocytesin vitroand in dogsin vivowere evaluated here. Incubation of primary human hepatocytes with TAF resulted in high levels of the pharmacologically active metabolite tenofovir diphosphate (TFV-DP), which persisted in the cell with a half-life of >24 h. In addition to passive permeability, studies of transfected cell lines suggest that the hepatic uptake of TAF is also facilitated by the organic anion-transporting polypeptides 1B1 and 1B3 (OATP1B1 and OATP1B3, respectively). In order to inhibit HBV reverse transcriptase, TAF must be converted to the pharmacologically active form, TFV-DP. While cathepsin A is known to be the major enzyme hydrolyzing TAF in cells targeted by HIV, including lymphocytes and macrophages, TAF was primarily hydrolyzed by carboxylesterase 1 (CES1) in primary human hepatocytes, with cathepsin A making a small contribution. Following oral administration of TAF to dogs for 7 days, TAF was rapidly absorbed. The appearance of the major metabolite TFV in plasma was accompanied by a rapid decline in circulating TAF. Consistent with thein vitrodata, high and persistent levels of TFV-DP were observed in dog livers. Notably, higher liver TFV-DP levels were observed after administration of TAF than those given TDF. These results support the clinical testing of once-daily low-dose TAF for the treatment of HBV infection.

scholarly journals Cytoplasmic Expression of the ALS/FTD-Related Protein TDP-43 Decreases Global Translation Both in vitro and in vivo

2020 ◽  
Vol 14 ◽  
Author(s):  
Santiago E. Charif ◽  
Luciana Luchelli ◽  
Antonella Vila ◽  
Matías Blaustein ◽  
Lionel M. Igaz
Keyword(s):  
De Novo ◽  
Brain Slices ◽  
Mrna Translation ◽  
Hek293 Cells ◽  
Cytoplasmic Inclusions ◽  
Cytoplasmic Expression ◽  
Global Translation

TDP-43 is a major component of cytoplasmic inclusions observed in neurodegenerative diseases like frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). To further understand the role of TDP-43 in mRNA/protein metabolism and proteostasis, we used a combined approach with cellular and animal models overexpressing a cytoplasmic form of human TDP-43 (TDP-43-ΔNLS), recapitulating ALS/FTD features. We applied in HEK293 cells a method for labeling de novo translation, surface sensing of translation (SUnSET), based on puromycin (PURO) incorporation. While control cells displayed robust puromycilation, TDP-43-ΔNLS transfected cells exhibited reduced ongoing protein synthesis. Next, by using a transgenic mouse overexpressing cytoplasmic TDP-43 in the forebrain (TDP-43-ΔNLS mice) we assessed whether cytoplasmic TDP-43 regulates global translation in vivo. Polysome profiling of brain cortices from transgenic mice showed a shift toward non-polysomal fractions as compared to wild-type littermates, indicating a decrease in global translation. Lastly, cellular level translational assessment by SUNSET was performed in TDP-43-ΔNLS mice brain slices. Control mice slices incubated with PURO exhibited robust cytoplasmic PURO signal in layer 5 neurons from motor cortex, and normal nuclear TDP-43 staining. Neurons in TDP-43-ΔNLS mice slices incubated with PURO exhibited high cytoplasmic expression of TDP-43 and reduced puromycilation respect to control mice. These in vitro and in vivo results indicate that cytoplasmic TDP-43 decreases global translation and potentially cause functional/cytotoxic effects as observed in ALS/FTD. Our study provide in vivo evidence (by two independent and complementary methods) for a role of mislocalized TDP-43 in the regulation of global mRNA translation, with implications for TDP-43 proteinopathies.

In vitro infection of primary human hepatocytes by HCV-positive sera: insights on a highly relevant model

Gut ◽  
2013 ◽  
Vol 63 (9) ◽  
pp. 1490-1500 ◽  
Author(s):  
Claire Gondeau ◽  
Philippe Briolotti ◽  
Francia Razafy ◽  
Cédric Duret ◽  
Pierre-Alain Rubbo ◽  
...  
Keyword(s):  
Human Hepatocytes ◽  
Relevant Model ◽  
Primary Human Hepatocytes

Long-term functional maintenance of primary human hepatocytes in vitro

Science ◽  
2019 ◽  
Vol 364 (6438) ◽  
pp. 399-402 ◽  
Author(s):  
Chengang Xiang ◽  
Yuanyuan Du ◽  
Gaofan Meng ◽  
Liew Soon Yi ◽  
Shicheng Sun ◽  
...  
Keyword(s):  
Cell Biology ◽  
Expression Profiles ◽  
Antiviral Drug ◽  
Gene Expression Profiles ◽  
Global Gene Expression ◽  
Human Hepatocytes ◽  
Hbv Infection ◽  
Primary Human Hepatocytes

The maintenance of terminally differentiated cells, especially hepatocytes, in vitro has proven challenging. Here we demonstrated the long-term in vitro maintenance of primary human hepatocytes (PHHs) by modulating cell signaling pathways with a combination of five chemicals (5C). 5C-cultured PHHs showed global gene expression profiles and hepatocyte-specific functions resembling those of freshly isolated counterparts. Furthermore, these cells efficiently recapitulated the entire course of hepatitis B virus (HBV) infection over 4 weeks with the production of infectious viral particles and formation of HBV covalently closed circular DNA. Our study demonstrates that, with a chemical approach, functional maintenance of PHHs supports long-term HBV infection in vitro, providing an efficient platform for investigating HBV cell biology and antiviral drug screening.

Sign in / Sign up

Export Citation Format

Share Document