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Glycogen synthase kinase-3beta activity plays very important roles in determining the fate of oxidative stress-inflicted neuronal cells.
Brain Res. 2007 Jan 19; 1129(1):89-99.BR

Abstract

Glycogen synthase kinase-3, especially the beta form (GSK-3beta), plays key roles in oxidative stress-induced neuronal cell death, an important pathogenic mechanism of various neurodegenerative diseases. Although the neuroprotective effects of GSK-3beta inhibitors have been described, the optimal level of GSK-3beta inhibition for neuronal cell survival has not yet been determined. We investigated the effect of varying GSK-3beta activity on the viability of oxidative stress-injured neuronally differentiated PC12 (nPC12) cells and intracellular signals related with the GSK-3beta and caspase-3 pathways. Compared to the nPC12 control cells treated with only 100 microM H(2)O(2), treatment of 50-200 nM GSK-3beta inhibitor II or 25-500 nM GSK-3beta inhibitor VIII reduced the increased enzyme activity by about 50% and protected the cells against H(2)O(2)-induced oxidative stress. The optimal concentration of GSK-3beta inhibitor II enhanced heat shock transcription factor-1 levels, decreased levels of phosphorylated tau (Ser202) and cytosolic cytochrome c, activated caspase-3, and cleaved poly (ADP-ribose) polymerase. In contrast, higher concentrations of GSK-3beta inhibitor II (more than 500 nM) induced neuronal cell death and showed opposite effects relative to the above described intracellular signals. These results suggest that optimized inhibitor levels for modulating GSK-3beta activity may prevent apoptosis induced by oxidative stress associated with neurodegenerative diseases.

Authors+Show Affiliations

Department of Neurology, Institute of Biomedical Science, College of Medicine, Hanyang University, Seoul, Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17157278

Citation

Lee, Kyu-Yong, et al. "Glycogen Synthase Kinase-3beta Activity Plays Very Important Roles in Determining the Fate of Oxidative Stress-inflicted Neuronal Cells." Brain Research, vol. 1129, no. 1, 2007, pp. 89-99.
Lee KY, Koh SH, Noh MY, et al. Glycogen synthase kinase-3beta activity plays very important roles in determining the fate of oxidative stress-inflicted neuronal cells. Brain Res. 2007;1129(1):89-99.
Lee, K. Y., Koh, S. H., Noh, M. Y., Park, K. W., Lee, Y. J., & Kim, S. H. (2007). Glycogen synthase kinase-3beta activity plays very important roles in determining the fate of oxidative stress-inflicted neuronal cells. Brain Research, 1129(1), 89-99.
Lee KY, et al. Glycogen Synthase Kinase-3beta Activity Plays Very Important Roles in Determining the Fate of Oxidative Stress-inflicted Neuronal Cells. Brain Res. 2007 Jan 19;1129(1):89-99. PubMed PMID: 17157278.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Glycogen synthase kinase-3beta activity plays very important roles in determining the fate of oxidative stress-inflicted neuronal cells. AU - Lee,Kyu-Yong, AU - Koh,Seong-Ho, AU - Noh,Min Young, AU - Park,Kun-Woo, AU - Lee,Young Joo, AU - Kim,Seung Hyun, Y1 - 2006/12/08/ PY - 2006/07/14/received PY - 2006/10/21/revised PY - 2006/10/26/accepted PY - 2006/12/13/pubmed PY - 2007/3/23/medline PY - 2006/12/13/entrez SP - 89 EP - 99 JF - Brain research JO - Brain Res VL - 1129 IS - 1 N2 - Glycogen synthase kinase-3, especially the beta form (GSK-3beta), plays key roles in oxidative stress-induced neuronal cell death, an important pathogenic mechanism of various neurodegenerative diseases. Although the neuroprotective effects of GSK-3beta inhibitors have been described, the optimal level of GSK-3beta inhibition for neuronal cell survival has not yet been determined. We investigated the effect of varying GSK-3beta activity on the viability of oxidative stress-injured neuronally differentiated PC12 (nPC12) cells and intracellular signals related with the GSK-3beta and caspase-3 pathways. Compared to the nPC12 control cells treated with only 100 microM H(2)O(2), treatment of 50-200 nM GSK-3beta inhibitor II or 25-500 nM GSK-3beta inhibitor VIII reduced the increased enzyme activity by about 50% and protected the cells against H(2)O(2)-induced oxidative stress. The optimal concentration of GSK-3beta inhibitor II enhanced heat shock transcription factor-1 levels, decreased levels of phosphorylated tau (Ser202) and cytosolic cytochrome c, activated caspase-3, and cleaved poly (ADP-ribose) polymerase. In contrast, higher concentrations of GSK-3beta inhibitor II (more than 500 nM) induced neuronal cell death and showed opposite effects relative to the above described intracellular signals. These results suggest that optimized inhibitor levels for modulating GSK-3beta activity may prevent apoptosis induced by oxidative stress associated with neurodegenerative diseases. SN - 0006-8993 UR - https://www.unboundmedicine.com/medline/citation/17157278/Glycogen_synthase_kinase_3beta_activity_plays_very_important_roles_in_determining_the_fate_of_oxidative_stress_inflicted_neuronal_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-8993(06)03186-6 DB - PRIME DP - Unbound Medicine ER -