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Babu Swathy, Moinak Banerjee
The diatheses of gene and environment interaction in schizophrenia (SCZ) are becoming increasingly evident. Genetic and epigenetic backgrounds are being considered in stratifying and addressing phenotypic variation and drug response in SCZ. But how much of these epigenetic alterations are the primary contributing factor, toward disease pathogenesis and drug response, needs further clarity. Evidence indicates that antipsychotic drugs can also alter the epigenetic homeostasis thereby inducing pharmacoepigenomic effects...
May 2017: Epigenomics
Babu Swathy, Koramannil R Saradalekshmi, Indu V Nair, Chandrasekharan Nair, Moinak Banerjee
AIM: It is imperative to differentiate the role of host epigenetics from pharmacoepigenetics in resolving therapeutic response. Therefore, the objective was to identify how antipsychotic drugs influence epigenetic response on pharmacogenes. MATERIALS & METHODS: The study design was based on in vitro evaluation of pharmacoepigenetic response of haloperidol, clozapine and olanzapine. Post antipsychotic treatment, the alterations in expression of ABCB1, CYP1A2 and CYP3A4 were monitored, and followed up by promoter methylation and their target miRNA expression studies...
April 21, 2017: Epigenomics
Manikandan Palrasu, Siddavaram Nagini
The cytochrome P450 (CYP) enzymes are membrane-bound hemoproteins that play a pivotal role in the detoxification of xenobiotics, cellular metabolism and homeostasis. Induction or inhibition of CYP enzymes is a major mechanism that underlies drug-drug interactions. CYP enzymes can be transcriptionally activated by various xenobiotics and endogenous substrates through receptor-dependent mechanisms. CYP enzyme inhibition is a principal mechanism for metabolism-based drug-drug interactions. Many chemotherapeutic drugs can cause drug interactions due to their ability to either inhibit or induce the CYP enzyme system...
January 25, 2017: Current Drug Targets
Aleksandra Majchrzak-Celińska, Wanda Baer-Dubowska
Epigenetics is a rapidly growing field describing heritable alterations in gene expression that do not involve DNA sequence variations. Advances in epigenetics and epigenomics have influenced pharmacology, leading to the development of a new specialty, pharmacoepigenetics, the study of the epigenetic basis for the individual variation in drug response. Areas covered: We present an overview of the major epigenetic mechanisms and their effects on the expression of drug metabolizing enzymes and drug transporters, as well as the epigenetic status of drug protein targets affecting therapy response...
April 2017: Expert Opinion on Drug Metabolism & Toxicology
Claudia Knothe, Bruno G Oertel, Alfred Ultsch, Mattias Kettner, Peter Harald Schmidt, Cora Wunder, Stefan W Toennes, Gerd Geisslinger, Jörn Lötsch
AIM: Exposure to opioids has been associated with epigenetic effects. Studies in rodents suggested a role of varying degrees of DNA methylation in the differential regulation of μ-opioid receptor expression across the brain. METHODS: In a translational investigation, using tissue acquired postmortem from 21 brain regions of former opiate addicts, representing a human cohort with chronic opioid exposure, μ-opioid receptor expression was analyzed at the level of DNA methylation, mRNA and protein...
December 2016: Epigenomics
Rihab Nasr, Fatima Sleiman, Zeinab Awada, Natalie K Zgheib
The focus of this manuscript is on DNA methylation and miRNA regulation of drug-metabolizing enzymes and drug transporters involved in the disposition of drugs commonly used in breast cancer. We start with a review of the available scant literature and follow with an in silico analysis of the CpG islands and miRNA binding sites of genes of interest. We make the case that there is room for further research to include more genes and miRNAs despite the extensive sharing of miRNA targets by candidate genes of interest...
September 2016: Pharmacogenomics
Stephen J Anderson, Kristina M Feye, Garrett R Schmidt-McCormack, Emir Malovic, Gregory S A Mlynarczyk, Patricia Izbicki, Larissa F Arnold, Matthew A Jefferson, Bierlein M de la Rosa, Rita F Wehrman, K C Luna, Hilary Z Hu, Naveen C Kondru, Michael D Kleinhenz, Joe S Smith, Sireesha Manne, Marson R Putra, Shivani Choudhary, Nyzil Massey, Diou Luo, Carrie A Berg, Sreemoyee Acharya, Shaunik Sharma, Sri Harsha Kanuri, Jennifer K Lange, Steve A Carlson
This review synthesizes examples of pharmacological agents who have off-target effects of an epigenetic nature. We expand upon the paradigm of epigenetics to include "quasi-epigenetic" mechanisms. Quasi-epigenetics includes mechanisms of drugs acting upstream of epigenetic machinery or may themselves impact transcription factor regulation on a more global scale. We explore these avenues with four examples of conventional pharmaceuticals and their unintended, but not necessarily adverse, biological effects. The quasi-epigenetic drugs identified in this review include the use of beta-lactam antibiotics to alter glutamate receptor activity and the action of cyclosporine on multiple transcription factors...
May 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Lorenzo Fornaro, Caterina Vivaldi, Chiara Caparello, Gianna Musettini, Editta Baldini, Gianluca Masi, Alfredo Falcone
Epigenetic mechanisms are involved in gastrointestinal (GI) cancer pathogenesis. Insights into the molecular basis of GI carcinogenesis led to the identification of different epigenetic pathways and signatures that may play a role as therapeutic targets in metastatic colorectal cancer (mCRC) and non-colorectal GI tumors. Among these alterations, O6-methylguanine DNA methyltransferase (MGMT) gene promoter methylation is the most investigated biomarker and seems to be an early and frequent event, at least in CRC...
2016: Frontiers in Bioscience (Elite Edition)
G Mátis, A Kulcsár, J Petrilla, K Hermándy-Berencz, Zs Neogrády
The expression of hepatic drug-metabolizing cytochrome P450 (CYP) enzymes may be affected by several nutrition-derived compounds, such as by the commonly applied feed additive butyrate, possibly leading to feed-drug interactions. The aim of this study was to provide some evidence if butyrate can alter the activity of hepatic CYPs in chickens exposed to CYP-inducing xenobiotics, monitoring for the first time the possibility of such interaction. Ross 308 chickens in the grower phase were treated with daily intracoelomal phenobarbital (PB) injection (80 mg/kg BW), applied as a non-specific CYP-inducer, simultaneously with two different doses of intra-ingluvial sodium butyrate boluses (0...
August 2016: Journal of Animal Physiology and Animal Nutrition
Mei-Mei Li, Balasubrahmanyam Addepalli, Mei-Juan Tu, Qiu-Xia Chen, Wei-Peng Wang, Patrick A Limbach, Janine M LaSalle, Su Zeng, Min Huang, Ai-Ming Yu
In contrast to the growing interests in studying noncoding RNAs (ncRNAs) such as microRNA (miRNA or miR) pharmacoepigenetics, there is a lack of efficient means to cost effectively produce large quantities of natural miRNA agents. Our recent efforts led to a successful production of chimeric pre-miR-27b in bacteria using a transfer RNA (tRNA)-based recombinant RNA technology, but at very low expression levels. Herein, we present a high-yield expression of chimeric pre-miR-1291 in common Escherichia coli strains using the same tRNA scaffold...
July 2015: Drug Metabolism and Disposition: the Biological Fate of Chemicals
M Ouni, M P Belot, A L Castell, D Fradin, P Bougnères
Short children using growth hormone (GH) to accelerate their growth respond to this treatment with a variable efficacy. The causes of this individual variability are multifactorial and could involve epigenetics. Quantifying the impact of epigenetic variation on response to treatments is an emerging challenge. Here we show that methylation of a cluster of CGs located within the P2 promoter of the insulin-like growth factor 1 (IGF1) gene, notably CG-137, is inversely closely correlated with the response of growth and circulating IGF1 to GH administration...
February 2016: Pharmacogenomics Journal
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