China
Africa
Explore chapters and articles related to this topic
Alternaria
Published in Dongyou Liu, Laboratory Models for Foodborne Infections, 2017
Alicia Rodríguez, Andrea Patriarca, Mar Rodríguez, María Jesús Andrade, Juan José Córdoba
The cell line Ishikawa allows examining the estrogenic potential of AOH.67 In this study, the estrogenicity of AOH was about 10,000-fold weaker than of the endogenous hormone E2. To identify if AOH may alter steroidogenesis, an in vitro screening assay based on measuring alterations in steroid hormone production and the expression of several important genes that encode the various enzymes involved in steroidogenesis using the human adrenocortical carcinoma cell line H295R has been performed by Frizzel et al.77 They demonstrated that AOH has the ability to interfere with steroidogenesis pathway since it modifies the expression of important genes in steroidogenesis in H295R cells.
Endocrine Glands
Published in Pritam S. Sahota, James A. Popp, Jerry F. Hardisty, Chirukandath Gopinath, Page R. Bouchard, Toxicologic Pathology, 2018
Richard A. Peterson, Sundeep Chandra, Mark J. Hoenerhoff
Once direct adrenocortical toxicity has been identified, the use of in vitro systems will be useful to investigate the precise mechanisms. The human adrenocortical carcinoma-derived cell line H295R has been widely used to study adrenocortical function, regulation of steroidogenesis, and screening of enzymatic inhibitors (Johansson et al. 2002; Sanderson et al. 2002; Müller-Vieira et al. 2005). This cell line expresses all the key enzymes necessary for steroidogenesis and the production of all the major steroids such as progesterone, androgens, estrogens, glucocorticoids, and the mineralocorticoid aldosterone (Zhang et al. 2005). In contrast to the human adrenal cortex in vivo, the H295R cells express aromatase and produce sex hormones such as testosterone and estradiol (Rainey et al. 1994). In the context of adrenal gland toxicology, though the priority is to identify compounds causing functional suppression of the adrenal gland, this in vitro cell line is used to detect upregulation as well as downregulation of steroidogenesis. Given that a number of the tested chemicals have been characterized as more or less specific inhibitors of the steroidogenic cytochrome P450 enzymes, it is not surprising that the general effect is toward inhibition of steroidogenesis and hormone secretion. The H295R in vitro system has a potential for high throughput screening not only to characterize the effects of chemicals on endocrine systems but also to prioritize chemicals for additional testing. The in vitro assay is generally useful for detecting direct effects on adrenal cells. A limitation of this model is that substances requiring metabolic activation or indirect effects on the adrenal gland due to disruption of the HPA axis cannot be adequately identified. In addition to H295R, a primary culture system of adrenocortical cells from dogs has been used. An added advantage of the canine system is a direct correlation to in vivo toxicology study data (Morishita et al. 2001).
Long Non-Coding RNA H19 Expression Correlates with Autophagy Process in Adrenocortical Carcinoma
Published in Cancer Investigation, 2022
Pietro Di Fazio, Franziska D. Rusche, Silvia Roth, Anika Pehl, Sabine Wächter, Ioannis Mintziras, Detlef K. Bartsch, Katharina Holzer
H295R cells were transiently knocked down for H19. As shown in Figure 4(B), H19 expression was significantly down-regulated after 48 h administration of two different short interference RNAs. The expression of the autophagy markers TFEB, BECN1, MAP1LC3B, UVRAG, SQSTM1, PRKAA1_1 and PRKAA2_1 was stable after H19 knockdown. The protein level of LC3B, Beclin1, DRAM1 and UVRAG was detected after administration of 100 nM of TSA, 10 µM of SAHA and 100 nM of panobinostat in H295R cells knocked down for H19. As shown in Figure 4(C), the knock down of H19 caused an accumulation of the autophagy markers, which was significantly higher than the protein level detected in H295R treated with DACi. The knock down of H19 was even able to cause an accumulation of almost all autophagy markers in the cells treated with 100 nM of panobinostat and 10 µM of SAHA. However, this accumulation could not be observed after the administration of TSA, which caused a significant down-regulation, probably acting independently of the H19 status. These results, confirmed by the densitometry and statistical (t-test) analysis (Figure 4(D)), highlighted that the expression of H19 contributes to the autophagy process. Its knock down most probably causes an accumulation of the autophagy proteins, which represents a block of the autophagic process.
In vitro modulation of multidrug resistance by pregnane steroids and in vivo inhibition of tumour development by 7α-OBz-11α(R)-OTHP-5β-pregnanedione in K562/R7 and H295R cell xenografts
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2019
Ghina Alameh, Agnès Emptoz-Bonneton, Marc Rolland de Ravel, Eva L. Matera, Elisabeth Mappus, Patrick Balaguer, Luc Rocheblave, Thierry Lomberget, Charles Dumontet, Marc Le Borgne, Michel Pugeat, Catherine Grenot, Claude Y. Cuilleron
In the present study, we report results of new biological investigations aimed at evaluating whether the nine progesterone and 5α/β-pregnane-3,20-dione MDR modulators 1–9 (Figure 1) previously selected using the K562/R7 cell line can maintain a high level of activity in vivo. In this view, three major obstacles could be expected for these compounds according to their structures: (i) the risks of metabolic deactivation by the enzymes of steroid metabolism, (ii) the potential hormonal side effects, (iii) the possibility of unacceptable levels of toxicity in vivo. These problems were successively addressed by comparative in vitro assays made on the human H295R adrenocortical carcinoma cell line rich in steroid metabolising enzymes and the metabolically inert K562/R7 cell line, by in vitro measurements of interactions with the human progesterone receptor (PR) and human pregnane X receptor (hPXR) and finally by in vivo assays made on mice xenografted with K562/R7 and NCI-H295R cell lines.
Steroid-resistant nephrotic syndrome: pharmacogenetics and epigenetic points and views
Published in Expert Review of Clinical Pharmacology, 2020
Seyede Mina Hejazian, Sepideh Zununi Vahed, Hakimeh Moghaddas Sani, Ziba Nariman-Saleh-Fam, Milad Bastami, Seyed Mahdi Hosseiniyan Khatibi, Mohammadreza Ardalan, Nasser Samadi
Several studies have implied post-transcriptional modifications induced by miRNAs in the regulation of GCs biosynthesis at different production levels [78–80]. miRNAs are 18–22 bp single-stranded noncoding RNAs which constitute 1% of the human genome. miRNAs are essential to regulate a wide range of cellular processes including organ development, inflammation and apoptosis. They interfere with the stability and translation of transcripts by targeting the 3ʹ-untranslated region (3ʹUTR) of mRNAs [81]. The involvement of miRNAs in all aspects of GC biology from GCs biosynthesis and availability to responses to therapy has been indicated [82]. Downregulation of Dicer, an enzyme involved in miRNA biosynthesis, in adrenocortical cells increased 11-beta-hydroxylase (encoded by CYP11B1) and aldosterone synthase (encoded by CYP11B2) expression through abrogating miRNA production [78]. 11-beta-hydroxylase plays a role in corticosterone and cortisol production in adrenal glands. Decreased expression of miR-24 in aldosterone-producing adenoma samples has been indicated. This microRNA binds to the 3ʹ UTR of CYP11B1 and CYP11B2 mRNAs and modulates their expression. This phenomenon will subsequently affect cortisol and aldosterone production [78]. In a similar investigation, further miRNAs targeting specific corticosteroidogenic genes in cortisol production pathways were recognized in H295R adrenocortical cells. The levels of CYP11B2 mRNAs were influenced by miR-125a-5p and miR-125b-5p and the levels of CYP11A1 and CYP17A1 mRNAs were changed by miR-320a-3p [83]. One transcript can be targeted by different miRNAs. For instance, CYP11B2 is negatively modulated by miR-10b, miR-24, miR125a-5p and miR-193a-3p [79,80,84]. In dexamethasone-treated HepaRG cells, miR-370 could degrade drug-metabolizing enzyme CYP2D6 mRNA, suggesting that miR-370 might be a potential mediator in drug–drug interaction through induction or inhibition of CYP2D6.