EGCG Attenuates CA1 Neuronal Death by Regulating GPx1, NF-κB S536 Phosphorylation and Mitochondrial Dynamics in the Rat Hippocampus following Status Epilepticus

Kim, Jieun; Kim, Tae Hyun; Kang, Tae‐Cheon

doi:10.3390/antiox12040966

Cited by 4 publications

(1 citation statement)

References 83 publications

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“…This ROS-mediated mechanism suggests the beneficial effects of antioxidants against aspartame-induced neurotoxicity. In addition, Kim et al [44] showed that epigallocatechin-3-gallate (EGCG), a clinically relevant antioxidant, attenuates neuronal death, accompanied by GPX1 induction and preserved mitochondria in neurons by activating the ERK1/2. MAPK.…”

Section: Antioxidants and Brain Healthmentioning

confidence: 99%

Cellular ROS and Antioxidants: Physiological and Pathological Role

Kozlov,

Javadov,

Sommer

2024

Antioxidants

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Section: Antioxidants and Brain Healthmentioning

confidence: 99%

Cellular ROS and Antioxidants: Physiological and Pathological Role

Kozlov,

Javadov,

Sommer

2024

Antioxidants

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Reciprocal regulation of oxidative stress and mitochondrial fission augments parvalbumin downregulation through CDK5-DRP1- and GPx1-NF-κB signaling pathways

Wang,

Lee,

Kim

et al. 2024

Cell Death Dis

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Loss of parvalbumin (PV) expressing neurons (PV neurons) is relevant to the underlying mechanisms of the pathogenesis of neurological and psychiatric diseases associated with the dysregulation of neuronal excitatory networks and brain metabolism. Although PV modulates mitochondrial morphology, volume and dynamics, it is largely unknown whether mitochondrial dynamics affect PV expression and what the molecular events are responsible for PV neuronal degeneration. In the present study, L-buthionine sulfoximine (BSO, an inhibitor of glutathione synthesis) did not degenerate PV neurons under physiological condition. However, BSO-induced oxidative stress decreased PV expression and facilitated cyclin-dependent kinase 5 (CDK5) tyrosine (Y) 15 phosphorylation, dynamin-related protein 1 (DRP1)-mediated mitochondrial fission and glutathione peroxidase-1 (GPx1) downregulation in PV neurons. Co-treatment of roscovitine (a CDK5 inhibitor) or mitochondrial division inhibitor-1 (Mdivi-1, an inhibitor of mitochondrial fission) attenuated BSO-induced PV downregulation. WY14643 (an inducer of mitochondrial fission) reduced PV expression without affecting CDK5 Y15 phosphorylation. Following status epilepticus (SE), CDK5 Y15 phosphorylation and mitochondrial fission were augmented in PV neurons. These were accompanied by reduced GPx1-mediated inhibition of NF-κB p65 serine (S) 536 phosphorylation. N-acetylcysteine (NAC), roscovitine and Mdivi-1 ameliorated SE-induced PV neuronal degeneration by mitigating CDK5 Y15 hyperphosphorylation, aberrant mitochondrial fragmentation and reduced GPx1-mediated NF-κB inhibition. Furthermore, SN50 (a NF-κB inhibitor) alleviated SE-induced PV neuronal degeneration, independent of dysregulation of mitochondrial fission, CDK5 hyperactivation and GPx1 downregulation. These findings provide an evidence that oxidative stress may activate CDK5-DRP1- and GPx1-NF-κB-mediated signaling pathways, which would be possible therapeutic targets for preservation of PV neurons in various diseases.

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Nicotinamide mononucleotide alleviates seizures via modulating SIRT1‐PGC‐1α mediated mitochondrial fusion and fission

Cheng,

Huang,

Zou

et al. 2024

Journal of Neurochemistry

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Both human and animal experiments have demonstrated that energy metabolism dysfunction in neurons after seizures is associated with an imbalance in mitochondrial fusion/fission dynamics. Effective neuronal mitochondrial dynamics regulation strategies remain elusive. Nicotinamide mononucleotide (NMN) can ameliorate mitochondrial functional and oxidative stress in age‐related diseases. But whether NMN improves mitochondrial energy metabolism to exert anti‐epileptic effects is unclear. This study aims to clarify if NMN can protect neurons from pentylenetetrazole (PTZ) or Mg2+‐free‐induced mitochondrial disorder and apoptosis via animal and cell models. We established a continuous 30‐day PTZ (37 mg/kg) intraperitoneal injection‐induced epileptic mouse model and a cell model induced by Mg2+‐free solution incubation to explore the neuroprotective effects of NMN. We found that NMN treatment significantly reduced the seizure intensity of PTZ‐induced epileptic mice, improved their learning and memory ability, and enhanced their motor activity and exploration desire. At the same time, in vitro and in vivo experiments showed that NMN can inhibit neuronal apoptosis and improve the mitochondrial energy metabolism function of neurons. In addition, NMN down‐regulated the expression of mitochondrial fission proteins (Drp1 and Fis1) and promoted the expression of mitochondrial fusion proteins (Mfn1 and Mfn2) by activating the SIRT1‐PGC‐1α pathway, thereby inhibiting PTZ or Mg2+‐free extracellular solution‐induced mitochondrial dysfunction, cell apoptosis, and oxidative stress. However, combined intervention of SIRT1 inhibitor, Selisistat, and PGC‐1α inhibitor, SR‐18292, eliminated the regulatory effect of NMN pre‐treatment on mitochondrial fusion and fission proteins and apoptosis‐related proteins. Therefore, NMN intervention may be a new potential treatment for cognitive impairment and behavioral disorders induced by epilepsy, and targeting the SIRT1‐PGC‐1α pathway may be a promising therapeutic strategy for seizures.

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EGCG Attenuates CA1 Neuronal Death by Regulating GPx1, NF-κB S536 Phosphorylation and Mitochondrial Dynamics in the Rat Hippocampus following Status Epilepticus

Cited by 4 publications

References 83 publications

Cellular ROS and Antioxidants: Physiological and Pathological Role

Cellular ROS and Antioxidants: Physiological and Pathological Role

Reciprocal regulation of oxidative stress and mitochondrial fission augments parvalbumin downregulation through CDK5-DRP1- and GPx1-NF-κB signaling pathways

Nicotinamide mononucleotide alleviates seizures via modulating SIRT1‐PGC‐1α mediated mitochondrial fusion and fission

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