Protein kinase A inhibitors enhance radiation-induced apoptosis

Journal of Cellular Biochemistry
D FindikM F Lavin

Abstract

In addition to a role for de novo protein synthesis in apoptosis we have previously shown that activation of a protein phosphatase or loss of activity of a kinase is also important in radiation-induced apoptosis in human cells [Baxter, and Lavin (1992): J Immunol 148:149-1954]. We show here that some inhibitors of protein kinases exacerbate radiation-induced apoptosis in the human cell line BM13674. The specific protein kinase A inhibitor isoquinoline sulfonamide (20 microM) gave rise to significantly increased levels of apoptosis at 2-6 h postirradiation compared to values after radiation exposure only. The same concentration of isoquinolinesulfonamide, which was effective in increasing apoptosis, reduced activity markedly. A 66% inhibition of cyclic AMP-dependent protein kinase A activity occurred in unirradiated cells at this concentration of H89 and activity was reduced to 58% in irradiated cells. Calphostin C, a specific inhibitor of protein kinase C, at a concentration of 0.1 microM, which caused 68% inhibition of enzyme activity in irradiated cells, failed to enhance the level of radiation-induced apoptosis. Other kinase inhibitors did not lead to an additional increase in apoptosis over and above that observed after irr...Continue Reading

References

Oct 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·F M UckunG L Schieven
Dec 1, 1992·Journal of Cellular Physiology·Q SongM F Lavin
Mar 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·D E HallahanR R Weichselbaum
Aug 1, 1991·Molecular and Cellular Biology·G P OwensJ J Cohen
Apr 1, 1990·Immunology Today·D J McConkeyM Jondal
Mar 15, 1989·Biochemical and Biophysical Research Communications·E KobayashiT Tamaoki
Nov 15, 1989·Biochemical and Biophysical Research Communications·G Rodríguez-Tarduchy, A López-Rivas
Jun 1, 1989·The Journal of Pathology·G D BaxterM F Lavin
Feb 11, 1988·Nucleic Acids Research·S A MillerH F Polesky
Jan 1, 1980·International Review of Cytology·A H WyllieA R Currie
Jan 15, 1993·Biochemical and Biophysical Research Communications·Q Song, M F Lavin
Jan 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·F M UckunC W Song

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Citations

Oct 31, 1996·Experientia·M F LavinQ Song
Sep 30, 2000·European Journal of Pharmacology·M BoardM A Cawthorne
Aug 1, 1997·Neurochemistry International·M H VarellaR Linden
Jan 6, 2000·The Biochemical Journal·S M JenkinsG V Johnson
Jan 29, 2000·The European Journal of Neuroscience·J L DupontJ de Barry
Jun 14, 2000·Cancer Biotherapy & Radiopharmaceuticals·R KumarI J Fidler
Jul 1, 2008·Oxidative Medicine and Cellular Longevity·Kenneth MaieseJinling Hou
Oct 18, 2000·Proceedings of the National Academy of Sciences of the United States of America·X FangG B Mills
Sep 5, 2009·Brain Research·Thuy-Vi V NguyenChristian J Pike
Jul 28, 2004·International Journal of Radiation Oncology, Biology, Physics·M Carmen Hernandez, Susan J Knox
Jan 8, 2004·Seminars in Oncology·M Carmen Hernandez, Susan J Knox
Apr 28, 2000·Gastroenterology·F SchliessD Häussinger
Aug 10, 2005·Journal of Cellular Biochemistry·James F Whitfield
Feb 19, 2002·Oncogene·Arturo P SaavedraJudy L Meinkoth
Aug 8, 1997·The Journal of Biological Chemistry·G WatanabeR G Pestell
Jan 16, 2007·American Journal of Physiology. Gastrointestinal and Liver Physiology·Christine SchäferFreimut Schliess
Oct 27, 1999·Developmental Dynamics : an Official Publication of the American Association of Anatomists·J X DiMario, P E Funk
Mar 2, 2013·American Journal of Physiology. Gastrointestinal and Liver Physiology·Lars HoffmannBernd C Schwahn
Jun 3, 1998·Molecular and Cellular Neurosciences·U SchmidtC Beyer

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis