Pyrroloquinoline quinone-conferred neuroprotection in rotenone models of Parkinson's disease.

Abstract

Pyrroloquinoline quinone (PQQ), a redox cofactor in the mitochondrial respiratory chain, has proven to protect neurons against glutamate-induced damage both in vitro and in vivo. This study was aimed to investigate the possible neuroprotective effects of PQQ in rotenone-induced Parkinson's disease (PD) model. Pre-treatment with PQQ prevented cultured SH-SY5Y cells from rotenone-induced apoptosis, accompanied by modulation of apoptosis-related proteins (Bcl-2, Bax and Smac), restoration of the mitochondrial membrane potential, inhibition of intracellular reactive oxygen species (ROS) production, suppression of tyrosine residues nitration, and dopamine redistribution. PQQ also exerted protective effects in an in vivo PD model, which was created by rotenone injection into the medial forebrain bundle of rats. Co-injection with PQQ and rotenone improved the apomorphine-evoked rotation, decreased neuronal loss, increased the ROS-scavenging ability, regulated intracellular expressions of mitochondrial complex subunits (Ndufs1-4), tyrosine hydroxylase, and vesicular monoamine transporter 2. Taken together, our results collectively suggest that PQQ confers neuroprotection in rotenone-induced PD model probably through complex and multifaceted mechanisms, at least involving oxidative stress, mitochondrial integrity, and dopamine functions.

• Authors: Jiaojiao Qin, Meilong Wu, Shu Yu, Xiaorong Gao, Jingjing Zhang, Xingyue Dong, Jinyan Ji, Yuxi Zhang, Lin Zhou, Qi Zhang, Fei Ding
• Journal: Toxicology letters (Toxicol Lett) Vol. 238 Issue 3 Pg. 70-82 (Nov 04 2015) ISSN: 1879-3169 [Electronic] Netherlands
• PMID: 26276080 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Antioxidants
• Neuroprotective Agents
• Slc18a2 protein, rat
• Vesicular Monoamine Transport Proteins
• Rotenone
• Malondialdehyde
• PQQ Cofactor
• Tyrosine 3-Monooxygenase
• Superoxide Dismutase
• Glutathione

Topics

• Animals
• Antioxidants (metabolism)
• Cell Line
• Cell Survival
• Gene Expression Regulation (drug effects)
• Glutathione
• Humans
• Malondialdehyde
• Neuroprotective Agents (pharmacology)
• PQQ Cofactor (pharmacology)
• Parkinson Disease, Secondary (chemically induced, prevention & control)
• Rats
• Rotenone (toxicity)
• Superoxide Dismutase
• Tyrosine 3-Monooxygenase (genetics, metabolism)
• Vesicular Monoamine Transport Proteins (genetics, metabolism)