The DOI matches its Crossref record; 24 of the 24 references it cites were found in a registry or an index.
The Mood‐Stabilizing Agent Valproate Inhibits the Activity of Glycogen Synthase Kinase‐3
Open accessAbstract
Abstract : Valproic acid (VPA) is a potent broad‐spectrum anti‐epileptic with demonstrated efficacy in the treatment of bipolar affective disorder. It has previously been demonstrated that both VPA and lithium increase activator protein‐1 (AP‐1) DNA binding activity, but the mechanisms underlying these effects have not been elucidated. However, it is known that phosphorylation of c‐jun by glycogen synthase kinase (GSK)‐3β inhibits AP‐1 DNA binding activity, and lithium has recently been demonstrated to inhibit GSK‐3β. These results suggest that lithium may increase AP‐1 DNA binding activity by inhibiting GSK‐3β. In the present study, we sought to determine if VPA, like lithium, regulates GSK‐3. We have found that VPA concentration‐dependently inhibits both GSK‐3α and ‐3β, with significant effects observed at concentrations of VPA similar to those attained clinically. Incubation of intact human neuroblastoma SH‐SY5Y cells with VPA results in an increase in the subsequent in vitro recombinant GSK‐3β‐mediated 32 P incorporation into two putative GSK‐3 substrates (~85 and 200 kDa), compatible with inhibition of endogenous GSK‐3β by VPA. Consistent with GSK‐3β inhibition, incubation of SH‐SY5Y cells with VPA results in a significant time‐dependent increase in both cytosolic and nuclear β‐catenin levels. GSK‐3β plays a critical role in the CNS by regulating various cytoskeletal processes as well as long‐term nuclear events and is a common target for both lithium and VPA ; inhibition of GSK‐3β in the CNS may thus underlie some of the long‐term therapeutic effects of mood‐stabilizing agents.
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Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B
Cross, D. A. E., Alessi, D. R., Cohen, P., Andjelkovich, M., & Hemmings, B. A. (1995) · Nature · doi:10.1038/378785a0 · Cited by 5,244
A molecular mechanism for the effect of lithium on development.
Klein, P. S., & Melton, D. A. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.16.8455 · Cited by 2,301
Lithium inhibits glycogen synthase kinase-3 activity and mimics wingless signalling in intact cells
Stambolic, V., Ruel, L., & Woodgett, J. R. (1996) · Current Biology · doi:10.1016/s0960-9822(02)70790-2 · Cited by 1,321
Ikeda, S. (1998) · The EMBO Journal · doi:10.1093/emboj/17.5.1371 · Cited by 1,246
Yost, C., Torres, M., Miller, J. R., Huang, E., Kimelman, D., & Moon, R. T. (1996) · Genes & Development · doi:10.1101/gad.10.12.1443 · Cited by 1,165
Activation of the Wnt Signaling Pathway: A Molecular Mechanism for Lithium Action
Hedgepeth, C. M., Conrad, L. J., Zhang, J., Huang, H.-C., Lee, V. M. Y., & Klein, P. S. (1997) · Developmental Biology · doi:10.1006/dbio.1997.8552 · Cited by 636
Initiation and adaptation: a paradigm for understanding psychotropic drug action
(1996) · American Journal of Psychiatry · doi:10.1176/ajp.153.2.151 · Cited by 490
Larabell, C. A., Torres, M., Rowning, B. A., Yost, C., Miller, J. R., Wu, M., Kimelman, D., & Moon, R. T. (1997) · The Journal of Cell Biology · doi:10.1083/jcb.136.5.1123 · Cited by 407
Differential regulation of glycogen synthase kinase-3 beta by protein kinase C isotypes.
Goode, N., Hughes, K., Woodgett, J. R., & Parker, P. J. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)41866-2 · Cited by 396
Signal Transduction Pathways: Molecular Targets for Lithium's Actions
Manji, H. K. (1995) · Archives of General Psychiatry · doi:10.1001/archpsyc.1995.03950190013003 · Cited by 328
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Cited by
Belmaker, R. H., & Agam, G. (2008) · New England Journal of Medicine · doi:10.1056/nejmra073096 · Cited by 2,166
GSK-3: tricks of the trade for a multi-tasking kinase
Doble, B. W., & Woodgett, J. R. (2003) · Journal of Cell Science · doi:10.1242/jcs.00384 · Cited by 2,084
Phiel, C. J., Zhang, F., Huang, E. Y., Guenther, M. G., Lazar, M. A., & Klein, P. S. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m101287200 · Cited by 1,758
Berk, M., Kapczinski, F., Andreazza, A. C., Dean, O. M., Giorlando, F., Maes, M., Yücel, M., Gama, C. S., Dodd, S., Dean, B., et al. (2011) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2010.10.001 · Cited by 1,178
Role of tau protein in both physiological and pathological conditions
AVILA, J., LUCAS, J. J., PÉREZ, M., & HERNÁNDEZ, F. (2004) · Physiological Reviews · doi:10.1152/physrev.00024.2003 · Cited by 1,005
Metadata
- Authors
- Chen, G., Huang, L., Jiang, Y., & Manji, H. K.
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2000-03
- Volume
- 72
- Issue
- 3
- Pages
- 1327-1330
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W2028494426
- Cited by
- 438
- References
- 24
- FWCI
- 16.93
- Type
- journal article
- Language
- en
- Open access
- bronze
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