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Activation of Akt kinase inhibits apoptosis and changes in Bcl-2 and Bax expression induced by nitric oxide in primary hippocampal neurons.
J Neurochem. 1999 Nov; 73(5):2037-46.JN

Abstract

Emerging data indicate that growth factors such as insulin-like growth factor-1 (IGF-1) prevent neuronal death due to nitric oxide (NO) toxicity. On the other hand, growth factors can promote cell survival by acting on phosphatidylinositol 3-kinase (PI3-kinase) and its downstream target, serine-threonine kinase Akt, in various types of cells. Here, we examined the mechanism by which IGF-1 inhibits neuronal apoptosis induced by NO in primary hippocampal neurons. IGF-1 was capable of preventing apoptosis and caspase-3-like activation induced by a NO donor, sodium nitroprusside or 3-morpholin-osydnonimine. Incubation of neurons with a P13-kinase inhibitor, wortmannin or LY294002, blocked the effects of IGF-1 on NO-induced neurotoxicity and caspase-3-like activation. In addition, the P13-kinase inhibitors blocked the effect of IGF-1 on down-regulation in Bcl-2 and upregulation in Bax expression induced by NO. Adenovirus-mediated overexpression of the activated form of Akt significantly inhibited NO-induced cell death, caspase-3-like activation, and changes in Bcl-2 and Bax expression. Moreover, expression of the kinase-defective form of Akt almost completely blocked the effects of IGF-1. These findings suggest that activation of Akt is necessary and sufficient for the effect of IGF-1 and is capable of preventing NO-induced apoptosis by modulating the NO-induced changes in Bcl-2 and Bax expression.

Authors+Show Affiliations

Department of Anatomy and Neuroscience, Osaka University Medical School, Japan.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

10537063

Citation

Matsuzaki, H, et al. "Activation of Akt Kinase Inhibits Apoptosis and Changes in Bcl-2 and Bax Expression Induced By Nitric Oxide in Primary Hippocampal Neurons." Journal of Neurochemistry, vol. 73, no. 5, 1999, pp. 2037-46.
Matsuzaki H, Tamatani M, Mitsuda N, et al. Activation of Akt kinase inhibits apoptosis and changes in Bcl-2 and Bax expression induced by nitric oxide in primary hippocampal neurons. J Neurochem. 1999;73(5):2037-46.
Matsuzaki, H., Tamatani, M., Mitsuda, N., Namikawa, K., Kiyama, H., Miyake, S., & Tohyama, M. (1999). Activation of Akt kinase inhibits apoptosis and changes in Bcl-2 and Bax expression induced by nitric oxide in primary hippocampal neurons. Journal of Neurochemistry, 73(5), 2037-46.
Matsuzaki H, et al. Activation of Akt Kinase Inhibits Apoptosis and Changes in Bcl-2 and Bax Expression Induced By Nitric Oxide in Primary Hippocampal Neurons. J Neurochem. 1999;73(5):2037-46. PubMed PMID: 10537063.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activation of Akt kinase inhibits apoptosis and changes in Bcl-2 and Bax expression induced by nitric oxide in primary hippocampal neurons. AU - Matsuzaki,H, AU - Tamatani,M, AU - Mitsuda,N, AU - Namikawa,K, AU - Kiyama,H, AU - Miyake,S, AU - Tohyama,M, PY - 1999/10/28/pubmed PY - 1999/10/28/medline PY - 1999/10/28/entrez SP - 2037 EP - 46 JF - Journal of neurochemistry JO - J Neurochem VL - 73 IS - 5 N2 - Emerging data indicate that growth factors such as insulin-like growth factor-1 (IGF-1) prevent neuronal death due to nitric oxide (NO) toxicity. On the other hand, growth factors can promote cell survival by acting on phosphatidylinositol 3-kinase (PI3-kinase) and its downstream target, serine-threonine kinase Akt, in various types of cells. Here, we examined the mechanism by which IGF-1 inhibits neuronal apoptosis induced by NO in primary hippocampal neurons. IGF-1 was capable of preventing apoptosis and caspase-3-like activation induced by a NO donor, sodium nitroprusside or 3-morpholin-osydnonimine. Incubation of neurons with a P13-kinase inhibitor, wortmannin or LY294002, blocked the effects of IGF-1 on NO-induced neurotoxicity and caspase-3-like activation. In addition, the P13-kinase inhibitors blocked the effect of IGF-1 on down-regulation in Bcl-2 and upregulation in Bax expression induced by NO. Adenovirus-mediated overexpression of the activated form of Akt significantly inhibited NO-induced cell death, caspase-3-like activation, and changes in Bcl-2 and Bax expression. Moreover, expression of the kinase-defective form of Akt almost completely blocked the effects of IGF-1. These findings suggest that activation of Akt is necessary and sufficient for the effect of IGF-1 and is capable of preventing NO-induced apoptosis by modulating the NO-induced changes in Bcl-2 and Bax expression. SN - 0022-3042 UR - https://www.unboundmedicine.com/medline/citation/10537063/Activation_of_Akt_kinase_inhibits_apoptosis_and_changes_in_Bcl_2_and_Bax_expression_induced_by_nitric_oxide_in_primary_hippocampal_neurons_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0022-3042&date=1999&volume=73&issue=5&spage=2037 DB - PRIME DP - Unbound Medicine ER -