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The neuroprotective action of pyrroloquinoline quinone against glutamate-induced apoptosis in hippocampal neurons is mediated through the activation of PI3K/Akt pathway.
Toxicol Appl Pharmacol. 2011 Apr 01; 252(1):62-72.TA

Abstract

Pyrroloquinoline quinone (PQQ), a cofactor in several enzyme-catalyzed redox reactions, possesses a potential capability of scavenging reactive oxygen species (ROS) and inhibiting cell apoptosis. In this study, we investigated the effects of PQQ on glutamate-induced cell death in primary cultured hippocampal neurons and the possible underlying mechanisms. We found that glutamate-induced apoptosis in cultured hippocampal neurons was significantly attenuated by the ensuing PQQ treatment, which also inhibited the glutamate-induced increase in Ca²+ influx, caspase-3 activity, and ROS production, and reversed the glutamate-induced decrease in Bcl-2/Bax ratio. The examination of signaling pathways revealed that PQQ treatment activated the phosphorylation of Akt and suppressed the glutamate-induced phosphorylation of c-Jun N-terminal protein kinase (JNK). And inhibition of phosphatidylinositol-3-kinase (PI3K)/Akt cascade by LY294002 and wortmannin significantly blocked the protective effects of PQQ, and alleviated the increase in Bcl-2/Bax ratio. Taken together, our results indicated that PQQ could protect primary cultured hippocampal neurons against glutamate-induced cell damage by scavenging ROS, reducing Ca²+ influx, and caspase-3 activity, and suggested that PQQ-activated PI3K/Akt signaling might be responsible for its neuroprotective action through modulation of glutamate-induced imbalance between Bcl-2 and Bax.

Authors+Show Affiliations

Jiangsu Key Laboratory of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, JS 226001, P.R. China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

21320517

Citation

Zhang, Qi, et al. "The Neuroprotective Action of Pyrroloquinoline Quinone Against Glutamate-induced Apoptosis in Hippocampal Neurons Is Mediated Through the Activation of PI3K/Akt Pathway." Toxicology and Applied Pharmacology, vol. 252, no. 1, 2011, pp. 62-72.
Zhang Q, Shen M, Ding M, et al. The neuroprotective action of pyrroloquinoline quinone against glutamate-induced apoptosis in hippocampal neurons is mediated through the activation of PI3K/Akt pathway. Toxicol Appl Pharmacol. 2011;252(1):62-72.
Zhang, Q., Shen, M., Ding, M., Shen, D., & Ding, F. (2011). The neuroprotective action of pyrroloquinoline quinone against glutamate-induced apoptosis in hippocampal neurons is mediated through the activation of PI3K/Akt pathway. Toxicology and Applied Pharmacology, 252(1), 62-72. https://doi.org/10.1016/j.taap.2011.02.006
Zhang Q, et al. The Neuroprotective Action of Pyrroloquinoline Quinone Against Glutamate-induced Apoptosis in Hippocampal Neurons Is Mediated Through the Activation of PI3K/Akt Pathway. Toxicol Appl Pharmacol. 2011 Apr 1;252(1):62-72. PubMed PMID: 21320517.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The neuroprotective action of pyrroloquinoline quinone against glutamate-induced apoptosis in hippocampal neurons is mediated through the activation of PI3K/Akt pathway. AU - Zhang,Qi, AU - Shen,Mi, AU - Ding,Mei, AU - Shen,Dingding, AU - Ding,Fei, Y1 - 2011/02/12/ PY - 2010/12/07/received PY - 2011/01/18/revised PY - 2011/02/04/accepted PY - 2011/2/16/entrez PY - 2011/2/16/pubmed PY - 2011/5/17/medline SP - 62 EP - 72 JF - Toxicology and applied pharmacology JO - Toxicol Appl Pharmacol VL - 252 IS - 1 N2 - Pyrroloquinoline quinone (PQQ), a cofactor in several enzyme-catalyzed redox reactions, possesses a potential capability of scavenging reactive oxygen species (ROS) and inhibiting cell apoptosis. In this study, we investigated the effects of PQQ on glutamate-induced cell death in primary cultured hippocampal neurons and the possible underlying mechanisms. We found that glutamate-induced apoptosis in cultured hippocampal neurons was significantly attenuated by the ensuing PQQ treatment, which also inhibited the glutamate-induced increase in Ca²+ influx, caspase-3 activity, and ROS production, and reversed the glutamate-induced decrease in Bcl-2/Bax ratio. The examination of signaling pathways revealed that PQQ treatment activated the phosphorylation of Akt and suppressed the glutamate-induced phosphorylation of c-Jun N-terminal protein kinase (JNK). And inhibition of phosphatidylinositol-3-kinase (PI3K)/Akt cascade by LY294002 and wortmannin significantly blocked the protective effects of PQQ, and alleviated the increase in Bcl-2/Bax ratio. Taken together, our results indicated that PQQ could protect primary cultured hippocampal neurons against glutamate-induced cell damage by scavenging ROS, reducing Ca²+ influx, and caspase-3 activity, and suggested that PQQ-activated PI3K/Akt signaling might be responsible for its neuroprotective action through modulation of glutamate-induced imbalance between Bcl-2 and Bax. SN - 1096-0333 UR - https://www.unboundmedicine.com/medline/citation/21320517/The_neuroprotective_action_of_pyrroloquinoline_quinone_against_glutamate_induced_apoptosis_in_hippocampal_neurons_is_mediated_through_the_activation_of_PI3K/Akt_pathway_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0041-008X(11)00052-4 DB - PRIME DP - Unbound Medicine ER -