A study on optimal concentrations of isodiospyrin putative inhibitory actions against exonic splicing enhancers of Dystrophin gene exon 53 skipping in Duchenne Muscular Dystrophy

Abstract

Event Abstract Back to Event A study on optimal concentrations of isodiospyrin putative inhibitory actions against exonic splicing enhancers of Dystrophin gene exon 53 skipping in Duchenne Muscular Dystrophy Hussain S. Alzahrani1*, Roslina Rashid2, Muzaimi Mustapha1 and Teguh H. Sasongko2 1 Universiti Sains Malaysia, Department of Neuroscience, School of Medical Sciences, Health Campus, Malaysia 2 Universiti Sains Malaysia, Human Genome Center, School of Medical Sciences, Health Campus, Malaysia Duchene muscular dystrophy (DMD) is an X-linked recessive disorder. It is characterized by rapid loss of muscular tissues due lacking gene of muscle replacement. The DMD gene is responsible for Dystrophin protein expression, which exists within a complex called Dystrophin glycol-protein complex (DGC). Exon mutations within DMD gene cause defective expression of Dystrophin. This study aimed to determine the inhibitory actions of Isodiospyrin targeting splicing factors and SR protein (Serine-arginine rich amino acids) a known topoisomerase inhibitor, which plays a critical role in splice site selection. previous studies demonstrated that Isodiospyrin has antitumor activity and inhibits topoisomerase enzyme from phosphorylating SF2/ASF splicing factor. In the current study we used plasmid of non-mutated exon 53 minigenes, transfected into non-mutated HEK-293 cell lines. Then, observed its actions on cells viability and exon splicing modification. The later was confirmed using RT-PCR, followed by exon 53 sequence software analysis. In consistence with previous studies, concentration of half maximal inhibitory effect (IC50) was 3.58µM, and the optimal inhibitory concentrations were: 1.79, 0.90, and 0.60µM. However, there was no detection of exon 53 skipping when exposing non-mutated HEK-293 cells to the optimal concentrations of Isodiospyrin compound. The results suggest that exon 53 splicing may occur without phosphorylation of SR proteins targeted by Isodiospyrin, which indicated that the splicing of exon 53 occurred independently of SR proteins targeted by the splicing inhibitor Isodiospyrin ,in non-mutated HEK-293 cells. Keywords: Gene Expression, inhibition, in vitro, Exon splicing, Duchenne muscular dystrophy Conference: 14th Meeting of the Asian-Pacific Society for Neurochemistry, Kuala Lumpur, Malaysia, 27 Aug - 30 Aug, 2016. Presentation Type: Poster Presentation Session Topic: 14th Meeting of the Asian-Pacific Society for Neurochemistry Citation: Alzahrani HS, Rashid R, Mustapha M and Sasongko TH (2016). A study on optimal concentrations of isodiospyrin putative inhibitory actions against exonic splicing enhancers of Dystrophin gene exon 53 skipping in Duchenne Muscular Dystrophy. Conference Abstract: 14th Meeting of the Asian-Pacific Society for Neurochemistry. doi: 10.3389/conf.fncel.2016.36.00120 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 04 Aug 2016; Published Online: 11 Aug 2016. * Correspondence: Mr. Hussain S Alzahrani, Universiti Sains Malaysia, Department of Neuroscience, School of Medical Sciences, Health Campus, Kota Bharu, Kelantan, 16150, Malaysia, hssz_23@hotmail.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Hussain S Alzahrani Roslina Rashid Muzaimi Mustapha Teguh H Sasongko Google Hussain S Alzahrani Roslina Rashid Muzaimi Mustapha Teguh H Sasongko Google Scholar Hussain S Alzahrani Roslina Rashid Muzaimi Mustapha Teguh H Sasongko PubMed Hussain S Alzahrani Roslina Rashid Muzaimi Mustapha Teguh H Sasongko Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.