title: Pyrroloquinoline quinine protects rat brain cortex against acute glutamate-induced neurotoxicity.
abstract: To investigate possible protective effects of pyrroloquinoline quinone (PQQ) on the rat cortex with glutamate injection and to understand the mechanisms linking the in vivo neuroprotection of PQQ. Adult Sprague-Dawley rats received glutamate injection into the rat cortex. Terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling assay was performed to observe influences of co-treatment with PQQ (simultaneous injection with PQQ and glutamate) on neural cell apoptosis in the rat cortex. The production of reactive oxygen species (ROS) in the rat cortex was detected by flow cytometry using 2',7'-dichlorofluorescin diacetate labeling, and the activity of superoxide dismutase, glutathione and malondialdehyde was respectively determined. Real time quantitative RT-PCR and Western blot were applied to measure the mRNA and protein expressions of Nrf1, Nrf2, HO-1 and GCLC in the rat cortex. Western blot was used to detect the phosphorylation of Akt and GSK3β in the rat cortex. Co-treatment with PQQ protected neural cells in the rat cortex from glutamate-induced apoptosis. PQQ decreased the ROS production induced by glutamate injection. PQQ increased the mRNA and protein expressions of Nrf2, HO-1 and GCLC and the phosphorylation of Akt and GSK3β in the cortex of glutamate-injected rats. PQQ could produce neuroprotective effects on the rat cortex. The antioxidant properties of PQQ and PQQ-induced activation of Akt/GSK3β signal pathway might be responsible for the in vivo neuroprotection of PQQ.
authors.affiliation: Jiangsu Key Laboratory of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, JS, 226001, People's Republic of China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.forename: Mei
authors.initials: M
authors.lastname: Ding
authors.forename: Zheng
authors.initials: Z
authors.lastname: Cao
authors.forename: Jingjing
authors.initials: J
authors.lastname: Zhang
authors.forename: Fei
authors.initials: F
authors.lastname: Ding
authors.forename: Kaifu
authors.initials: K
authors.lastname: Ke
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001483:Base Sequence; D002540:Cerebral Cortex / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D017931:DNA Primers; D018698:Glutamic Acid / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010766:Phosphorylation; D011758:Pyrroles / Q000494:pharmacology*; D011804:Quinolines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D017931:DNA Primers; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D011758:Pyrroles; D011804:Quinolines; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C410406:pyrroloquinoline; D018698:Glutamic Acid; D008315:Malondialdehyde; D013482:Superoxide Dismutase; D005978:Glutathione