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Cyclin D1, cdk4, and Bim are involved in thrombin-induced apoptosis in cultured cortical neurons.
J Neurochem 2007; 101(2):498-505JN

Abstract

Thrombin, a multifunctional serine protease, is neurotoxic in vitro and in vivo. Thrombin has been shown to be increased in Alzheimer's disease (AD) and other neuropathological conditions and could be a mediator of pathological neuronal cell death in the brain. The mechanisms of thrombin-induced neuronal cell death are incompletely understood. The objective of this study is to explore mechanisms that contribute to thrombin-induced neuronal apoptosis focusing on the role of cell cycle regulators and the pro-apoptotic protein Bim (Bcl-2-interacting mediator of cell death) in this process. Our data show that thrombin treatment of primary cerebral cortical cultures results in dose-dependent apoptotic cell death. Exposure of neuronal cultures to thrombin leads to induction of cell cycle proteins cyclin D1 and cyclin E, at both mRNA and protein levels. In addition, thrombin treatment causes the appearance of cyclin-dependent kinase 4 (cdk4) and expression of the pro-apoptotic protein Bim. Inhibition of cdk4 prevents both induction of Bim expression and thrombin-induced neuronal apoptosis. These data demonstrate that thrombin-induced apoptosis proceeds via cell cycle activation involving cdk4 resulting in induction of Bim. Thus, cell cycle proteins could be therapeutic targets in diseases such as AD where thrombin has been implicated.

Authors+Show Affiliations

Garrison Institute on Aging and Department of Neuropsychiatry and Behavioral Sciences, Texas Tech University Health Sciences Center, Lubbock, Texas 79430, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17254021

Citation

Rao, Haripriya Vittal, et al. "Cyclin D1, Cdk4, and Bim Are Involved in Thrombin-induced Apoptosis in Cultured Cortical Neurons." Journal of Neurochemistry, vol. 101, no. 2, 2007, pp. 498-505.
Rao HV, Thirumangalakudi L, Desmond P, et al. Cyclin D1, cdk4, and Bim are involved in thrombin-induced apoptosis in cultured cortical neurons. J Neurochem. 2007;101(2):498-505.
Rao, H. V., Thirumangalakudi, L., Desmond, P., & Grammas, P. (2007). Cyclin D1, cdk4, and Bim are involved in thrombin-induced apoptosis in cultured cortical neurons. Journal of Neurochemistry, 101(2), pp. 498-505.
Rao HV, et al. Cyclin D1, Cdk4, and Bim Are Involved in Thrombin-induced Apoptosis in Cultured Cortical Neurons. J Neurochem. 2007;101(2):498-505. PubMed PMID: 17254021.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cyclin D1, cdk4, and Bim are involved in thrombin-induced apoptosis in cultured cortical neurons. AU - Rao,Haripriya Vittal, AU - Thirumangalakudi,Lakshmi, AU - Desmond,Paula, AU - Grammas,Paula, Y1 - 2007/01/24/ PY - 2007/1/27/pubmed PY - 2007/6/2/medline PY - 2007/1/27/entrez SP - 498 EP - 505 JF - Journal of neurochemistry JO - J. Neurochem. VL - 101 IS - 2 N2 - Thrombin, a multifunctional serine protease, is neurotoxic in vitro and in vivo. Thrombin has been shown to be increased in Alzheimer's disease (AD) and other neuropathological conditions and could be a mediator of pathological neuronal cell death in the brain. The mechanisms of thrombin-induced neuronal cell death are incompletely understood. The objective of this study is to explore mechanisms that contribute to thrombin-induced neuronal apoptosis focusing on the role of cell cycle regulators and the pro-apoptotic protein Bim (Bcl-2-interacting mediator of cell death) in this process. Our data show that thrombin treatment of primary cerebral cortical cultures results in dose-dependent apoptotic cell death. Exposure of neuronal cultures to thrombin leads to induction of cell cycle proteins cyclin D1 and cyclin E, at both mRNA and protein levels. In addition, thrombin treatment causes the appearance of cyclin-dependent kinase 4 (cdk4) and expression of the pro-apoptotic protein Bim. Inhibition of cdk4 prevents both induction of Bim expression and thrombin-induced neuronal apoptosis. These data demonstrate that thrombin-induced apoptosis proceeds via cell cycle activation involving cdk4 resulting in induction of Bim. Thus, cell cycle proteins could be therapeutic targets in diseases such as AD where thrombin has been implicated. SN - 0022-3042 UR - https://www.unboundmedicine.com/medline/citation/17254021/Cyclin_D1_cdk4_and_Bim_are_involved_in_thrombin_induced_apoptosis_in_cultured_cortical_neurons_ L2 - https://doi.org/10.1111/j.1471-4159.2006.04389.x DB - PRIME DP - Unbound Medicine ER -