A new class of molecular targeted radioprotectors: GSK-3beta inhibitors.

International Journal of Radiation Oncology, Biology, Physics
Dinesh K ThotalaEugenia M Yazlovitskaya

Abstract

Development of new treatments is critical to effective protection against radiation-induced injury. We investigate the potential of developing small-molecule inhibitors of glycogen synthase kinase 3beta (GSK-3beta)-SB216763 or SB415286-as radioprotective agents to attenuate intestinal injury. A survival study was done by use of C57BL/6J mice to evaluate the radioprotective effect of GSK-3beta inhibitors. Terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay and immunohistochemical staining for Bax and Bcl-2 were used to assess apoptosis in the small intestines of the treated mice. A clonogenic survival study, apoptosis assays (staining with annexin V or 4',6-diamidino-2-phenylindole), and immunoblot analysis of beta-catenin, Bcl-2, Bax, and caspase 3 were done by use of Rat intestinal epithelial cell line IEC-6 cells. Pretreatment with SB415286 significantly improved survival of mice irradiated with 8 and 12 Gy. Mice pretreated with SB216763 or SB415286 showed a significant reduction in TUNEL- and Bax-positive cells and an increase in Bcl-2-positive cells in intestinal crypts at 4 and/or 12 h after radiation with 4 and/or 8 Gy compared with radiation alone. Pretreatment of irradiated IEC-6 cells with GSK-3...Continue Reading

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Jun 23, 2009·Free Radical Biology & Medicine·Dinesh ThotalaEugenia Yazlovitskaya

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Citations

Jun 22, 2013·Cell Death & Disease·E M YazlovitskayaA V Ivanova
Mar 21, 2013·Molecular Therapy : the Journal of the American Society of Gene Therapy·Szilvia AranyCatherine E Ovitt
Feb 18, 2011·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Dong XiWen-Jun Gao
Jun 8, 2012·International Journal of Cell Biology·Keith M JacobsDinesh Thotala
May 2, 2014·Journal of Controlled Release : Official Journal of the Controlled Release Society·Reine-Solange SauerHeike L Rittner
Feb 2, 2012·The British Journal of Radiology·M I Koukourakis
May 3, 2011·Expert Opinion on Biological Therapy·Patrick MaierFrederik Wenz
Feb 20, 2015·Cell Death & Disease·E M YazlovitskayaA V Ivanova
Feb 22, 2012·International Journal of Radiation Oncology, Biology, Physics·Bo HaiFei Liu
Feb 1, 2015·Biochemical and Biophysical Research Communications·Jiawen DaiRajamanickam Baskar
Mar 28, 2017·SLAS Discovery·Svenja LeyHeinz Ruffner
Jan 12, 2019·Radiation Oncology Journal·Vinutha Kuruba, Pavan Gollapalli
Jul 19, 2011·American Journal of Physiology. Lung Cellular and Molecular Physiology·Yasuhiro TerasakiYuh Fukuda
Jan 26, 2016·Medicinal Research Reviews·Mohammad Zahid KamranVibha Tandon
Oct 1, 2011·The Journal of Pathology·Agnieszka KaczmarekDmitri V Krysko
Aug 20, 2020·American Journal of Physiology. Gastrointestinal and Liver Physiology·Chethan SampathPandu R Gangula
Dec 28, 2018·Cell Death Discovery·Maria Rita FabbriziGirdhar G Sharma
Nov 5, 2020·Biomedicines·Elena ObradorAlegría Montoro
Apr 2, 2014·Journal of Cell Science·Ulrich MaurerCéline Charvet
Jun 29, 2021·Free Radical Research·Rahul CheckerSantosh K Sandur

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