The neuroprotective action of pyrroloquinoline quinone against glutamate-induced apoptosis in hippocampal neurons is mediated through the activation of PI3K/Akt pathway

Zhang, Qi; Shen, Mi; Ding, Mei; Shen, Dingding; Ding, Fei

doi:10.1016/j.taap.2011.02.006

Cited by 41 publications

(27 citation statements)

References 75 publications

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“…PQQ treatment following glutamate stimulation rescued neurite damage and promoted the translocation of Nrf2 from the cytoplasm to nucleus ( Figure 2D). We previously demonstrated that PI3K/Akt inhibition by LY294002 or wortmannin significantly blocked the protective effects of PQQ (Zhang et al, 2011). In this study, we found that these two PI3K inhibitors also blocked the influence of PQQ on Nrf2 translocation, implying that PI3K/Akt activation was required for the nuclear translocation of Nrf2 in glutamate-injured hippocampal neurons ( Figure 2E and F).…”

Section: Pqq Activated the Phosphorylation Of Akt/gsk3β Pathwaysupporting

confidence: 62%

“…PQQ treatment can rescue primary cultured hippocampal neurons from glutamate injury (Zhang et al, 2011). For further elucidation of mechanisms involved, this study showed that PQQ treatment following glutamate stimulation led to the sustained activation of Akt and downstream phosphorylation of GSK3β, promoted the PI3K/Akt pathway-dependent nuclear translocation of transcription factor Nrf2, and resulted in the up-regulation of mRNA expression of transcription factor Nrf2 and antioxidant enzyme genes, HO-1 and GCLC, which was also dependent on the activation of the PI3K/Akt pathway.…”

Section: Discussionmentioning

confidence: 99%

“…Our previous study showed that treatment with 50 or 100 μM PQQ for 30 min could significantly increase the phosphorylated Akt level in glutamate-injured hippocampal neurons (Zhang et al, 2011). In this study, we treated glutamate-injured hippocampal neurons with 100 μM PQQ for different times (5 and 30 min, and 2, 4, and 24 h), and investigated whether the activation of Akt was transient or sustained.…”

Section: Pqq Activated the Phosphorylation Of Akt/gsk3β Pathwaymentioning

confidence: 93%

“…Hippocampal neurons were harvested from E18.5 Sprague-Dawley (SD) rat embryos (obtained from the Experimental Animal Center of Nantong University, China) exactly as described previously (Zhang et al, 2011). Briefly, the rat brain was dissected to collect the hippocampi, which were subjected to digestion with 0.25% trypsin in Ca 2+ -and Mg 2+ -free Hank's balanced salt solution at 37°C for 10 min.…”

Section: Cell Culture and Cell Treatmentmentioning

confidence: 99%

“…PQQ has been found to modulate N-methyl-D-aspartate (NMDA) receptor by directly oxidizing its redox modulatory site and to inhibit glutamateinduced ROS production in cultured cortical neurons (Aizenman et al, 1992;Scanlon et al, 1997). Our recent research demonstrated that PQQ could rescue primary hippocampal neurons from glutamate injury through inhibition of ROS production and activation of the phosphatidylinositol-3-kinase (PI3K)/Akt pathway (Zhang et al, 2011). However, the downstream pathways and the details of molecular mechanisms involved have not been fully elucidated.…”

Section: Introductionmentioning

confidence: 99%

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

Zhang¹,

Ding²,

Gao³

et al. 2012

Genet. Mol. Res.

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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.

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Section: Pqq Activated the Phosphorylation Of Akt/gsk3β Pathwaysupporting

confidence: 62%

Section: Discussionmentioning

confidence: 99%

Section: Pqq Activated the Phosphorylation Of Akt/gsk3β Pathwaymentioning

confidence: 93%

Section: Cell Culture and Cell Treatmentmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

Zhang¹,

Ding²,

Gao³

et al. 2012

Genet. Mol. Res.

View full text Add to dashboard Cite

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Deep Learning‐Driven Exploration of Pyrroloquinoline Quinone Neuroprotective Activity in Alzheimer's Disease

Li,

Sun,

Zhou

et al. 2024

Advanced Science

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Alzheimer's disease (AD) is a pressing concern in neurodegenerative research. To address the challenges in AD drug development, especially those targeting Aβ, this study uses deep learning and a pharmacological approach to elucidate the potential of pyrroloquinoline quinone (PQQ) as a neuroprotective agent for AD. Using deep learning for a comprehensive molecular dataset, blood–brain barrier (BBB) permeability is predicted and the anti‐inflammatory and antioxidative properties of compounds are evaluated. PQQ, identified in the Mediterranean‐DASH intervention for a diet that delays neurodegeneration, shows notable BBB permeability and low toxicity. In vivo tests conducted on an Aβ₁₋₄₂‐induced AD mouse model verify the effectiveness of PQQ in reducing cognitive deficits. PQQ modulates genes vital for synapse and anti‐neuronal death, reduces reactive oxygen species production, and influences the SIRT1 and CREB pathways, suggesting key molecular mechanisms underlying its neuroprotective effects. This study can serve as a basis for future studies on integrating deep learning with pharmacological research and drug discovery.

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Targeting mitochondrial alterations to prevent type 2 diabetes—Evidence from studies of dietary redox‐active compounds

Cheng

Schmelz

Liu

et al. 2014

Molecular Nutrition Food Res

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As a growing epidemic, type 2 diabetes mellitus (T2DM) has significantly affected the individual's quality of life and economy of the society. Understanding the mechanisms of the disease and discovery of new therapeutic options has become more urgent than ever before. Mitochondrial alterations (e.g. functional alterations, and impaired biogenesis and dynamics) are strongly associated with the development of T2DM. Accumulation of reactive oxygen species or intermediates of incomplete fatty acid oxidation due to mitochondrial deficiency activates stress kinases and dampens insulin signaling. Redox-active compounds such as resveratrol, pyrroloquinoline quinone, and hydroxytyrosol can potently counteract reactive oxygen species, and improve mitochondrial function and biogenesis. Therefore, targeting the mitochondrial alterations with these redox-active compounds may lead to new therapeutic or preventive options for T2DM. In this article, we review the molecular mechanisms of mitochondrial alterations in T2DM, and the action of redox-active compounds to reverse mitochondrial changes and oxidative stress in T2DM. In addition, the current challenges and future directions are discussed and prospected.

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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

Cited by 41 publications

References 75 publications

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

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

Deep Learning‐Driven Exploration of Pyrroloquinoline Quinone Neuroprotective Activity in Alzheimer's Disease

Targeting mitochondrial alterations to prevent type 2 diabetes—Evidence from studies of dietary redox‐active compounds

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