Expression and activity of P‐glycoprotein (MDR1/ABCB1) in peripheral blood mononuclear cells from patients with anorexia nervosa compared with healthy controls

Storch, Caroline Henrike; Nikendei, Christoph; Schild, Sandra; Haefeli, Walter E.; Weiß, Johanna; Herzog, Wolfgang

doi:10.1002/eat.20519

Cited by 6 publications

(4 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Janas-Kozik et al (2008) found that a leptin receptor transcript showed statistically significant differences between individuals with AN and controls. Several other investigations compared expression of P-glycoprotein (Storch et al, 2008) and prohormone preproenkephalin (Weiss et al, 2010), failed to find significant differences. Although limited in number, these studies have provided some preliminary information regarding transcriptomic profiling in AN.…”

Section: Introductionmentioning

confidence: 99%

Assessment of gene expression in peripheral blood using RNAseq before and after weight restoration in anorexia nervosa

Kim

Trace

Crowley

et al. 2013

Psychiatry Research

View full text Add to dashboard Cite

We examined gene expression in the blood of six females with anorexia nervosa (AN) before and after weight restoration using RNAseq. AN cases (aged 19-39) completed clinical assessments and had blood drawn for RNA at hospital admission (T1, < ~75% ideal body weight, IBW) and again at discharge (T2, ≥ ~85% IBW). To examine the relationship between weight restoration and differential gene expression, normalized gene expression levels were analyzed using a paired design. We found 564 genes whose expression was nominally significantly different following weight restoration (p < 0.01, 231 increased and 333 decreased). With a more stringent significance threshold (false discovery rate q < 0.05), 67 genes met criteria for differential expression. Of the top 20 genes, CYP11A1, C16orf11, LINC00235, and CPA3 were down-regulated more than two-fold after weight restoration while multiple olfactory receptor genes (OR52J3, OR51L1, OR51A4, OR51A2) were up-regulated more than two-fold after weight restoration. Pathway analysis revealed up-regulation of two broad pathways with largely overlapping genes, one related to protein secretion and signaling and the other associated with defense response to bacterial regulation. Although results are preliminary secondary to a small sample size, these data provide initial evidence of transcriptional alterations during weight restoration in AN.

show abstract

Section: Introductionmentioning

confidence: 99%

Assessment of gene expression in peripheral blood using RNAseq before and after weight restoration in anorexia nervosa

Kim

Trace

Crowley

et al. 2013

Psychiatry Research

View full text Add to dashboard Cite

show abstract

“…Of various in vitro assays to measure the efflux ratio [ 39 , 40 , 41 , 42 ], the monolayer efflux assay is the most relevant to drug distribution and the most commonly used in practice [ 20 ], in which the polarized epithelial cells, such as Madin–Darby canine kidney (MDCK) cells, are transfected with the MDR1 gene, followed by measuring the ratios between basolateral-to-apical (B→A) apparent permeability ( P app ) and apical-to-basolateral (A→B) P app [ 43 ].

where P app is evaluated using the membrane surface area ( A ), initial dosing concentration of the test molecule ( C 0 ) in the donor compartment, and the amount of molecule transported per time ( dQ / dt ) in the receiver compartment [ 44 ]. Normally, molecules with ER > 2 are classified as P-gp substrates [ 39 ].…”

Section: Introductionmentioning

confidence: 99%

Theoretical Prediction of the Complex P-Glycoprotein Substrate Efflux Based on the Novel Hierarchical Support Vector Regression Scheme

et al. 2018

View full text Add to dashboard Cite

P-glycoprotein (P-gp), a membrane-bound transporter, can eliminate xenobiotics by transporting them out of the cells or blood–brain barrier (BBB) at the expense of ATP hydrolysis. Thus, P-gp mediated efflux plays a pivotal role in altering the absorption and disposition of a wide range of substrates. Nevertheless, the mechanism of P-gp substrate efflux is rather complex since it can take place through active transport and passive permeability in addition to multiple P-gp substrate binding sites. A nonlinear quantitative structure–activity relationship (QSAR) model was developed in this study using the novel machine learning-based hierarchical support vector regression (HSVR) scheme to explore the perplexing relationships between descriptors and efflux ratio. The predictions by HSVR were found to be in good agreement with the observed values for the molecules in the training set (n = 50, r2 = 0.96, qCV2 = 0.94, RMSE = 0.10, s = 0.10) and test set (n = 13, q2 = 0.80–0.87, RMSE = 0.21, s = 0.22). When subjected to a variety of statistical validations, the developed HSVR model consistently met the most stringent criteria. A mock test also asserted the predictivity of HSVR. Consequently, this HSVR model can be adopted to facilitate drug discovery and development.

show abstract

“…Kahl et al observed an increase in TNF-α and IL-6 expression in AN at hospital admission time compared with controls, and TNF-α remained significantly higher while IL-6 expression decreased in weight-restored patients (Kahl et al, 2004). In studies on expression of P-glycoprotein (Storch et al, 2008) and prohormone preproenkephalin (ppE mRNA) (Weiss et al, 2010), neither study could identify evidence to support a significant difference between AN and healthy controls, although ppE mRNA level was negatively associated with depressive and anxious symptoms (Weiss et al, 2010). …”

Section: Alteration Of Gene Expression: Mrna and Methylationmentioning

confidence: 99%

Contemporary views on the genetics of anorexia nervosa

Shih

Woodside

2016

European Neuropsychopharmacology

View full text Add to dashboard Cite

Anorexia nervosa (AN) is a serious mental illness characterized by severe dietary restriction that leads to high rates of morbidity, chronicity, and mortality. Unfortunately, effective treatment is lacking and few options are available. High rates of familial aggregation and significant heritability suggested that the complex etiology of AN is affected by both genetic and environmental factors. In this paper, we review studies that reported common and rare genetic variation that influence susceptibility of AN through candidate gene studies, genome-wide association studies, and sequencing-based studies. We also discuss gene expression, methylation, imaging genetics, and pharmacogenetics to demonstrate that these studies have collectively advanced our knowledge of how genetic variation contributes to AN susceptibility and clinical course. Lastly, we highlight the importance of gene by environment interactions (G x E) and share our enthusiasm for the use of nutritional genomic approaches to elucidate the interaction among nutrients, metabolic intermediates, and genetic variation in AN. A deeper understanding of how nutrition alters genome stability, how genetic variation influences uptake and metabolism of nutrients, and how response to food components affects disordered eating, will lead to personalized dietary interventions and effective nutraceutical and pharmacological treatments for AN.

show abstract

Expression and activity of P‐glycoprotein (MDR1/ABCB1) in peripheral blood mononuclear cells from patients with anorexia nervosa compared with healthy controls

Abstract: Failure in pharmacotherapy with P-gp substrates in AN patients are probably neither caused by different P-gp expression nor activity levels.

Cited by 6 publications

References 46 publications

Assessment of gene expression in peripheral blood using RNAseq before and after weight restoration in anorexia nervosa

Assessment of gene expression in peripheral blood using RNAseq before and after weight restoration in anorexia nervosa

Theoretical Prediction of the Complex P-Glycoprotein Substrate Efflux Based on the Novel Hierarchical Support Vector Regression Scheme

Contemporary views on the genetics of anorexia nervosa

Contact Info

Product

Resources

About