Abstract
The purpose of this study was to examine whether glycogen synthase kinase-3 (GSK-3) is involved in colchicine-induced cell death in PC12 cells by using GSK inhibitors. Colchicine increased apoptotic cell death with morphological changes characterized by cell shrinkage and nuclear condensation or fragmentation. GSK-3 inhibitors such as alsterpaullone, SB216763, and AR-A014418 prevented colchicine-induced cell death and caspase-3 activation. These results suggest that colchicine induces caspase-dependent apoptotic cell death and that GSK-3 activation is involved in cell death in PC12 cells.
Similar content being viewed by others
References
Alnemri ES, Livingston DJ, Nicholson DW, Salvesen G, Thornberry NA, Wong WW, Yuan J (1996) Human ICE/CED-3 protease nomenclature. Cell 87:171
Bhat R, Xue Y, Berg S, Hellberg S, Ormö M, Nilsson Y, Radesäter A-C, Jerning E, Markgren P-O, Borgegård T, Nylöf M, Giménez-Cassina A, Hernández F, Lucas JJ, Díaz-Nido J, Avila J (2003) Structural insights and biological effects of glycogen synthase kinase 3-specific inhibitor AR-A014418. J Biol Chem 278:45937–45945
Black MM, Aletta JM, Greene LA (1986) Regulation of microtubule composition and stability during nerve growth factor-promoted neurite outgrowth. J Cell Biol 103:545–557
Bonfoco E, Ceccatelli S, Manzo L, Nicotera P (1995) Colchicine induces apoptosis in cerebellar granule cells. Exp Cell Res 218:189–200
Coghlan MP, Culbert AA, Cross DA (2000) Selective small molecule inhibitors of glycogen synthase kinase-3 modulate glycogen metabolism and gene transcription. Chem Biol 7:793–803
Cross DA, Alessi DR, Cohen P, Andjelkovich M, Hemmings BA (1995) Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B. Nature 378:785–789
Dudek H, Datta SR, Franke TF, Birnbaum MJ, Yao R, Cooper GM, Segal RS, Kaplan DR, Greenberg ME (1997) Regulation of neuronal survival by the serine-threonine protein kinase Akt. Science 275:661–665
Gorman AM, Bonfoco E, Zhivotovsky B (1999) Cytochrome c release and caspase-3 activation during colchicine-induced apoptosis of cerebellar granule cells. Eur J Neurosci 11:1067–1072
Greene LA, Tischler AS (1976) Establishment of a noradrenergic clonal line of rat adrenal pheochromocytoma cells which respond to nerve growth factor. Proc Natl Acad Sci USA 73:2424–2428
Grimes CA, Jope RS (2001) The multifaceted roles of glycogen synthase kinase 3beta in cellular signaling. Prog Neurobiol 65:391–426
Habas A, Kharebava G, Szatmari E, Hetman M (2006) NMDA neuroprotection against a phosphatidylinositol-3 kinase inhibitor, LY294002 by NR2B-mediated suppression of glycogen synthase kinase-3β-induced apoptosis. J Neurochem 96:335–348
Hetman M, Cavanaugh JE, Kimelman D (2000) Role of glycogen synthase kinase-3beta in neuronal apoptosis induced by trophic withdrawal. J Neurosci 20:2567–2574
Johnson BD, Byerly L (1993) A cytoskeletal mechanism for Ca2+ channel metabolic dependence and inactivation by intracellular Ca2+. Neuron 10:797–804
Jope RS, Johnson GV (2004) The glamour and gloom of glycogen synthase kinase-3. Trends Biochem Sci 29:95–102
Jordà EG, Verdaguer E, Jimenez A, Arriba SG, Allgaier C, Pallàs M, Camins A (2005) Evaluation of the neuronal apoptotic pathways involved in cytoskeletal disruption-induced apoptosis. Biochem Pharmacol 70:470–480
Kim R, Emi M, Tanabe K, Murakami S (2006) Role of the unfolded protein response in cell death. Apoptosis 11:5–13
Koh JY, Choi DW (1987) Quantitative determination of glutamate mediated cortical neuronal injury in cell culture by lactate dehydrogenase efflux assay. J Neurosci Methods 20:83–90
Linseman DA, Butts BD, Precht TA, Phelps RA, Le SS, Laessig TA, Bouchard RJ, Florez-McClure ML, Heidenreich KA (2004) Glycogen synthase kinase-3beta phosphorylates Bax and promotes its mitochondrial localization during neuronal apoptosis. J Neurosci 24:9993–10002
Nakagawa Y, Nakamura S, Kase Y, Noguchi T, Ishihara T (1987) Colchicine lesions in the rat hippocampus mimic the alterations of several markers in Alzheimer’s disease. Brain Res 408:57–64
Nicholson DW, Ali A, Thornberry NA et al (1995) Identification and inhibition of the ICE/CED-3 protease necessary for mammalian apoptosis. Nature 376:37–43
Pap M, Cooper GM (1998) Role of glycogen synthase kinase-3 in the phosphatidylinositol 3-Kinase/Akt cell survival pathway. J Biol Chem 273:19929–19932
Seng S, Avraham HK, Jiang S, Venkatesh S, Avraham S (2006) KLHL1/MRP2 mediates neurite outgrowth in a glycogen synthase kinase 3beta-dependent manner. Mol Cell Biol 26:8371–8384
Takadera T, Ohyashiki T (1997) Apoptotic cell death and caspase 3 (CPP32) activation induced by calcium ionophore at low concentrations and their prevention by nerve growth factor in PC12 cells. Eur J Biochem 249:8–12
Takadera T, Ohyashiki T (2007) Calmodulin inhibitor-induced apoptosis was prevented by glycogen synthase kinase-3 inhibitors in PC12 cells. Cell Mol Neurobiol 27:783–790
Takadera T, Sakamoto Y, Ohyashiki T (2004) NMDA receptor 2B-selective antagonist ifenprodil-induced apoptosis was prevented by glycogen synthase kinase-3 inhibitors in cultured rat cortical neurons. Brain Res 1020:196–203
Thoenen H, Barde YA (1980) Physiology of nerve growth factor. Physiol Rev 60:1284–1335
Wienecke A, Bacher G (2009) Indibulin, a novel microtubule inhibitor, discriminates between mature neuronal and nonneuronal tubulin. Cancer Res 69:171–177
Yao R, Cooper GM (1995) Requirement for phosphatidylinositol-3 kinase in the prevention of apoptosis by nerve growth factor. Science 267:2003–2006
Yip HK, Rich KM, Lampe PA, Johnson EM Jr (1984) The effects of nerve growth factor and its antiserum on the postnatal development and survival after injury of sensory neurons in rat dorsal root ganglia. J Neurosci 4:2986–2992
Acknowledgments
This study was supported in part by a special in-house research grant from Hokuriku University.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Takadera, T., Nakajima, Y. & Kanai, Y. Colchicine-Induced Apoptosis Was Prevented by Glycogen Synthase Kinase-3 Inhibitors in PC12 Cells. Cell Mol Neurobiol 30, 863–868 (2010). https://doi.org/10.1007/s10571-010-9514-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10571-010-9514-z