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PI3K/Akt signaling pathway is required for neuroprotection of thalidomide on hypoxic-ischemic cortical neurons in vitro.
Brain Res. 2010 Oct 21; 1357:157-65.BR

Abstract

Thalidomide, a derivative of glutamic acid, is used for immunomodulatory therapy in various diseases through inhibition of tumor necrotic factor-α (TNF-α) release. However, the effects of thalidomide in central nervous system (CNS) diseases such as stroke or hypoxic-ischemic encephalopathy (HIE) are unknown. In this study, we aimed to test whether thalidomide protects against hypoxic-ischemic neuronal damage and the possible signaling pathway involved in neuroprotection. Primary cultured cortical neurons of rats were treated with oxygen and glucose deprivation (OGD) for 3h to mimic hypoxic-ischemic injury in vivo. Neuronal apoptosis was measured with terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining. The expression of total caspase-3 (C3), cleaved caspase-3 (CC3), Akt, phosphorylated-Akt (p-Akt) and Bcl-2 protein were detected by Western blots. We found that OGD treatment increased the expression of CC3 and induced neuronal apoptosis. Both neuronal apoptosis and CC3 expression peaked at 24h after OGD. Furthermore, we found that thalidomide protected neurons against apoptosis by decreasing CC3 and increasing Bcl-2 expression in a dose-dependent manner. Meanwhile, we found that thalidomide induced p-Akt expression, which could be inhibited by PI3K specific inhibitor, LY294002. In addition, inhibition of PI3K increased CC3 but decreased Bcl-2 expression. In summary, thalidomide has anti-apoptotic effects on cortical neurons after OGD by modulating CC3 and Bcl-2 expression through activation of PI3K/Akt pathway.

Authors+Show Affiliations

Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, China.No affiliation info availableNo 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

20705061

Citation

Zhang, Li, et al. "PI3K/Akt Signaling Pathway Is Required for Neuroprotection of Thalidomide On Hypoxic-ischemic Cortical Neurons in Vitro." Brain Research, vol. 1357, 2010, pp. 157-65.
Zhang L, Qu Y, Tang J, et al. PI3K/Akt signaling pathway is required for neuroprotection of thalidomide on hypoxic-ischemic cortical neurons in vitro. Brain Res. 2010;1357:157-65.
Zhang, L., Qu, Y., Tang, J., Chen, D., Fu, X., Mao, M., & Mu, D. (2010). PI3K/Akt signaling pathway is required for neuroprotection of thalidomide on hypoxic-ischemic cortical neurons in vitro. Brain Research, 1357, 157-65. https://doi.org/10.1016/j.brainres.2010.08.007
Zhang L, et al. PI3K/Akt Signaling Pathway Is Required for Neuroprotection of Thalidomide On Hypoxic-ischemic Cortical Neurons in Vitro. Brain Res. 2010 Oct 21;1357:157-65. PubMed PMID: 20705061.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - PI3K/Akt signaling pathway is required for neuroprotection of thalidomide on hypoxic-ischemic cortical neurons in vitro. AU - Zhang,Li, AU - Qu,Yi, AU - Tang,Jun, AU - Chen,Dapeng, AU - Fu,Xuemei, AU - Mao,Meng, AU - Mu,Dezhi, Y1 - 2010/08/10/ PY - 2010/07/02/received PY - 2010/07/31/revised PY - 2010/08/04/accepted PY - 2010/8/14/entrez PY - 2010/8/14/pubmed PY - 2011/1/15/medline SP - 157 EP - 65 JF - Brain research JO - Brain Res VL - 1357 N2 - Thalidomide, a derivative of glutamic acid, is used for immunomodulatory therapy in various diseases through inhibition of tumor necrotic factor-α (TNF-α) release. However, the effects of thalidomide in central nervous system (CNS) diseases such as stroke or hypoxic-ischemic encephalopathy (HIE) are unknown. In this study, we aimed to test whether thalidomide protects against hypoxic-ischemic neuronal damage and the possible signaling pathway involved in neuroprotection. Primary cultured cortical neurons of rats were treated with oxygen and glucose deprivation (OGD) for 3h to mimic hypoxic-ischemic injury in vivo. Neuronal apoptosis was measured with terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining. The expression of total caspase-3 (C3), cleaved caspase-3 (CC3), Akt, phosphorylated-Akt (p-Akt) and Bcl-2 protein were detected by Western blots. We found that OGD treatment increased the expression of CC3 and induced neuronal apoptosis. Both neuronal apoptosis and CC3 expression peaked at 24h after OGD. Furthermore, we found that thalidomide protected neurons against apoptosis by decreasing CC3 and increasing Bcl-2 expression in a dose-dependent manner. Meanwhile, we found that thalidomide induced p-Akt expression, which could be inhibited by PI3K specific inhibitor, LY294002. In addition, inhibition of PI3K increased CC3 but decreased Bcl-2 expression. In summary, thalidomide has anti-apoptotic effects on cortical neurons after OGD by modulating CC3 and Bcl-2 expression through activation of PI3K/Akt pathway. SN - 1872-6240 UR - https://www.unboundmedicine.com/medline/citation/20705061/PI3K/Akt_signaling_pathway_is_required_for_neuroprotection_of_thalidomide_on_hypoxic_ischemic_cortical_neurons_in_vitro_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-8993(10)01754-3 DB - PRIME DP - Unbound Medicine ER -