Prevention of rat cortical neurons from prostaglandin E2-induced apoptosis by glycogen synthase kinase-3 inhibitors

Neuroscience Letters
Tsuneo Takadera, Takao Ohyashiki

Abstract

Cyclooxygenase-2 (COX-2) induction and prostaglandin E(2) (PGE(2)) elevation have been reported to occur after cerebral ischemic insult. PGE(2) induces apoptosis through the PGE(2) EP2 receptor by a cAMP-dependent pathway. Glycogen synthase kinase-3 (GSK-3) affects many fundamental cellular functions. We examined whether GSK-3 is involved in PGE(2)-induced cell death by using GSK-3 inhibitors in rat cultured cortical neurons. Cells treated with 12.5 microM PGE(2) for 2 days shrank. The injured cells underwent chromatin condensation and nuclear fragmentation detected by staining with Hoechst33258, indicating apoptotic cell death. We assayed the effects of selective GSK-3 inhibitors SB216763 and alsteropaullone on PGE(2)-induced apoptosis. These inhibitors completely protected the cells from apoptosis induced by PGE(2). Moreover, dibutyryl cAMP (a cell permeable cAMP)-induced apoptosis was also prevented by alsteropaullone. In addition, GSK-3 inhibitors inhibited caspase-3 activation accompanied by PGE(2)-induced apoptosis. We showed in this report that PGE(2)-induced apoptosis is prevented by GSK-3 inhibitors, suggesting that PGE(2) induces caspase-dependent apoptosis mediated through GSK-3 activation in rat cultured cortical ne...Continue Reading

References

Jan 1, 1993·Acta Neuropathologica·M O DereskiJ H Garcia
Aug 1, 1998·The Journal of Biological Chemistry·M Pap, G M Cooper
Aug 11, 1999·Trends in Neurosciences·U DirnaglM A Moskowitz
Feb 7, 2001·Proceedings of the National Academy of Sciences of the United States of America·C IadecolaM E Ross
Jan 5, 2002·Neuroscience Letters·Tsuneo TakaderaTakao Ohyashiki
Jun 18, 2002·The Journal of Pharmacology and Experimental Therapeutics·Marina S FeschenkoKathleen J Sweadner
Jan 13, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Louise McCulloughKatrin Andreasson

❮ Previous
Next ❯

Citations

Sep 11, 2007·Apoptosis : an International Journal on Programmed Cell Death·Sévan KaloustianGuy Rousseau
Mar 10, 2011·Acta Physiologica·P A InselA C Zambon
Dec 15, 2015·Biochimica Et Biophysica Acta·Ana B Fernández-MartínezFrancisco J Lucio Cazaña
Jun 5, 2007·Neuroscience and Biobehavioral Reviews·Adam R ColeCalum Sutherland
May 23, 2014·Brain Research·Takayuki NaganoMotohiko Takemura
Feb 9, 2008·American Journal of Physiology. Gastrointestinal and Liver Physiology·Satish RamalingamShrikant Anant
Mar 31, 2021·Scientific Reports·Coral García-PastorFrancisco J Lucio-Cazaña

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptotic Caspases

Apoptotic caspases belong to the protease enzyme family and are known to play an essential role in inflammation and programmed cell death. Here is the latest research.

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