Pyrroloquinoline quinone rescues hippocampal neurons from glutamate-induced cell death through activation of Nrf2 and up-regulation of antioxidant genes

Abstract

ABSTRACT. Pyrroloquinoline quinone (PQQ) has been shown to protect primary cultured hippocampal neurons from glutamateinduced cell apoptosis by scavenging reactive oxygen species (ROS) and activating phosphatidylinositol-3-kinase (PI3K)/Akt signaling. We investigated the downstream pathways of PI3K/Akt involved in PQQ protection of glutamate-injured hippocampal neurons. Western blot analysis indicated that PQQ treatment following glutamate stimulation triggers phosphorylation of glycogen synthase kinase 3β, accompanied by maintenance of Akt activation. Immunostaining and quantitative RT-PCR revealed that PQQ treatment promotes nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2), and up-regulates mRNA expression of Nrf2 and the antioxidant enzyme genes, heme oxygenase-1 and glutamate cysteine ligase catalytic in glutamate-injured hippocampal neurons; this is a process dependent on the PI3K/Akt pathway, as evidenced by blocking experiments with PI3K inhibitors. In addition, increased ROS production and decreased glutathione ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 11 (3): 2652-2664 (2012) PQQ rescues neurons from death through Nrf2 activation 2653 levels in glutamate-injured hippocampal neurons were found to be reduced by PQQ treatment. Collectively, our findings suggest that PQQ exerts neuroprotective activity, possibly through PI3K/Akt-dependent activation of Nrf2 and up-regulation of antioxidant genes. However, the ability of PQQ to scavenge ROS was not totally regulated by PI3K/Akt signaling; possibly it is governed by other mechanisms.

Effect of pyrroloquinoline quinone disodium in female rats during gestating and lactating on reproductive performance and the intestinal barrier functions in the progeny

“…In our study, an increase in CAT and SOD was observed (P < 0•05) with dietary PQQ•Na 2 supplementation in the placenta. A previous study has demonstrated that SOD activity can be up-regulated by PQQ•Na 2 treatment (44) , and this is consistent with our study results. GSH is one of the most important molecules in mammalian cells for scavenging ROS.…”

Quercetin Protects against Lipopolysaccharide-Induced Intestinal Oxidative Stress in Broiler Chickens through Activation of Nrf2 Pathway

“…Quercetin (98%, Changyue biological techology, Xi'an, China) was mixed in the basal diet. On day 16,18, and 20 of the 21-day feeding trial, broiler chickens in the LPS, Que200+LPS, and Que500+LPS groups received an intraperitoneal LPS challenge (E. coli serotype 055: B55; Sigma, Saint Louis, MO, USA). The LPS injection volume was 0.5 mg/kg bodyweight (diluted with sterilized saline to 0.5 mg/mL) at 500 µg/mL/kg dissolved in sterile saline.…”

“…The redox-sensitive nuclear factor erythroid 2-related factor 2 (Nrf2) transcription factor is the main defense mechanism against various harmful stresses; it improves the body's antioxidant status and maintains cellular redox homeostasis [15,16]. Nrf2 can regulate downstream antioxidants to exert stronger protective effects, including heme oxygenase-1 (HO-1), NAD(P)H dehydrogenase quinone 1 (NQO1), and superoxide dismutase (SOD) [17,18]. However, the involvement of Nrf2 signaling in the effects of quercetin on intestinal oxidative stress in broiler chickens is yet to be verified.…”

Pyrroloquinoline quinone against glutamate‐induced neurotoxicity in cultured neural stem and progenitor cells

“…As an essential nutrient, PQQ has been proven to play important roles in the regulation of cellular growth and development in mammalian system, and is therefore expected to be applied pharmacologically in the near future (He et al, 2003; Misra et al, 2012). Many studies in recent years have shown that PQQ functions as an antioxidant protecting the living cells from oxidative damage in vivo and the biomolecules from artificially produced ROS in vitro for supporting the growth and protection of living cells under stress (Gong et al, 2012; Zhang et al, 2012a,b). As we know, ROS production is greatly increased under many conditions of toxic stress and plays an important role in brain injuries and some neurodegenerative diseases (Rashid et al, 2013).…”