scholarly journals Pink1 protects cortical neurons from thapsigargin-induced oxidative stress and neuronal apoptosis

2015 ◽  
Vol 35 (1) ◽  
Author(s):  
Lin Li ◽  
Guo-ku Hu
Keyword(s):  
Oxidative Stress ◽  
Cortical Neurons ◽  
Neuronal Apoptosis ◽  
Physiological Role ◽  
Cultured Neurons ◽  
Mitochondrial Oxidative Stress

Pink1 (PTEN-induced kinase 1) have a physiological role in mitochondrial maintenance, suppressing mitochondrial oxidative stress, fission, and autophagy. Our findings indicated that thapsigargin induced oxidative stress and neuronal apoptosis in cultured neurons is at least partly mediated inactivation of Pink1.

CREB Protects against Temporal Lobe Epilepsy Associated with Cognitive Impairment by Controlling Oxidative Neuronal Damage

2019 ◽  
Vol 19 (5-6) ◽  
pp. 225-237 ◽  
Author(s):  
Jihong Xing ◽  
Dongfeng Han ◽  
Dahai Xu ◽  
Xingliang Li ◽  
Lichao Sun
Keyword(s):  
Oxidative Stress ◽  
Cognitive Impairment ◽  
Temporal Lobe Epilepsy ◽  
Cognitive Dysfunction ◽  
Neuronal Apoptosis ◽  
Neuronal Damage ◽  
Primary Neurons ◽  
Mitochondrial Oxidative Stress ◽  
Memory Decline ◽  
Downstream Signaling

Background: Cognitive dysfunction as a common comorbidity of epilepsy often manifests as learning and memory impairments in patients with temporal lobe epilepsy (TLE). The pathogenetic molecular mechanisms underlying epilepsy-associated cognitive dysfunction are incompletely understood. We investigated the role of cAMP response element binding protein (CREB) and its downstream signaling pathways in the pathogenesis of cognitive impairment in mice with TLE. Methods: Plasmid vectors of CREB-specific short-hairpin RNAs and CREB cDNA were prepared and transfected into primary neurons. Neuronal apoptosis and mitochondrial oxidative stress were assessed by flow cytometry. For in vivo studies, TLE in mice was induced by pilocarpine injection, and TLE-associated memory decline was evaluated using the Morris water maze after treatment with the CREB inhibitor 666-15, with or without the mitochondria-specific antioxidant MitoQ. CREB and its downstream mediators were examined by Western blotting analysis and quantitative reverse transcription polymerase chain reaction. Results: CREB knockdown induced mitochondrial reactive oxygen species production and apoptosis in primary neurons whereas CREB overexpression brought the opposite effects. The TLE mice exhibited elevated oxidative stress and neuronal apoptosis with decreased expression of CREB and its downstream mediators including PKA, CaMKIV, arc, and c-fos. CREB inhibition exacerbated TLE-associated oxidative neuronal apoptosis and memory decline. MitoQ treatment restored the expression of CREB and its downstream mediators, and prevented TLE-associated oxidative neuronal damage and memory deficits aggravated by CREB inhibition. Conclusion: CREB plays a significant role in TLE-associated oxidative neuronal damage and memory impairment. This novel finding provides the evidence of the relationship between CREB and mitochondrial oxidative stress and cognitive dysfunction in epilepsy. Mitochondria-specific antioxidants such as MitoQ may alleviate TLE-associated cognitive dysfunction through activation of CREB and its downstream signaling pathways.

scholarly journals Neuroprotective Effect of Physical Exercise on Neuronal Apoptosis Induced by Tramadol in Cerebral Cortex of Rats

2020 ◽  
Vol 10 (6) ◽  
pp. 7209-7222
Keyword(s):  
Oxidative Stress ◽  
Cerebral Cortex ◽  
Physical Exercise ◽  
Cortical Neurons ◽  
Neuronal Apoptosis ◽  
Neuroprotective Effect ◽  
Physiological Saline ◽  
Male Rats ◽  
Control Group ◽  
Oxidative Stress Biomarkers

Tramadol is a centrally acting analgesic agent with low affinity for opioid receptors, used for treating moderate to severe pain. Tramadol, like other opioids, induces neuronal apoptosis, which causes multiple neuronal impairments. The current study was conducted to evaluate the potential neuroprotective role of physical exercises on tramadol-induced neuronal apoptosis in the cerebral cortex of rats. Thirty adult male rats were divided into three groups (n= 10) as follow; the control group was gavaged with physiological saline (0.9% NaCl); tramadol group was daily administered with tramadol (40 mg/kg) for 28 days, and physical exercise group was administered with the same dose as tramadol group, then rats were forced to run on the treadmill for 30 min, once a day for 28 days. Tramadol induced histopathological changes in the form of neuroses degeneration and apoptosis. These findings were confirmed by immunohistochemical and blotting studies, which showed upregulation of p53 and downregulation of Bcl-2. In addition, malondialdehyde (MDA), myeloperoxidase (MPO), and nuclear factor kappa B (NF-κB) significantly increased following tramadol administration. At the same time, glutathione (GSH) and glutathione peroxidase (GPx) were decreased. In contrast, physical exercise was found to protect cortical neurons from degeneration and apoptosis produced by tramadol. This was evidenced by the downregulation of p53 and upregulating Bcl-2 expression and the improved changes in the oxidative stress biomarkers in rats. Physical exercise reduced the neuronal apoptosis and degeneration in the cerebral cortex following tramadol administration through suppressing oxidative stress.

Lycopene Prevents Amyloid [Beta]-Induced Mitochondrial Oxidative Stress and Dysfunctions in Cultured Rat Cortical Neurons

2016 ◽  
Vol 41 (6) ◽  
pp. 1354-1364 ◽  
Author(s):  
Mingyue Qu ◽  
Zheng Jiang ◽  
Yuanxiang Liao ◽  
Zhenyao Song ◽  
Xinzhong Nan
Keyword(s):  
Oxidative Stress ◽  
Amyloid Beta ◽  
Cortical Neurons ◽  
Mitochondrial Oxidative Stress ◽  
Rat Cortical Neurons

scholarly journals Ubiquitin-Specific Protease 29 Exacerbates Cerebral Ischemia-Reperfusion Injury in Mice

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Jia-Bao Hou ◽  
Qian-Ni Shen ◽  
Xing Wan ◽  
Xu-Ke Liu ◽  
Yuan Yu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cortical Neurons ◽  
Neuronal Apoptosis ◽  
Ischemia Reperfusion ◽  
Primary Cortical Neurons ◽  
Cerebral Ischemia Reperfusion ◽  
Specific Protease ◽  
Ubiquitin Specific Protease ◽  
The Brain

Oxidative stress and apoptosis contribute to the progression of cerebral ischemia/reperfusion (I/R) injury. Ubiquitin-specific protease 29 (USP29) is abundantly expressed in the brain and plays critical roles in regulating oxidative stress and cell apoptosis. The purpose of the present study is to investigate the role and underlying mechanisms of USP29 in cerebral I/R injury. Neuron-specific USP29 knockout mice were generated and subjected to cerebral I/R surgery. For USP29 overexpression, mice were stereotactically injected with the adenoassociated virus serotype 9 vectors carrying USP29 for 4 weeks before cerebral I/R. And primary cortical neurons were isolated and exposed to oxygen glucose deprivation/reperfusion (OGD/R) stimulation to imitate cerebral I/R injury in vitro. USP29 expression was elevated in the brain and primary cortical neurons upon I/R injury. Neuron-specific USP29 knockout significantly diminished, whereas USP29 overexpression aggravated cerebral I/R-induced oxidative stress, apoptosis, and neurological dysfunction in mice. In addition, OGD/R-induced oxidative stress and neuronal apoptosis were also attenuated by USP29 silence but exacerbated by USP29 overexpression in vitro. Mechanistically, neuronal USP29 enhanced p53/miR-34a-mediated silent information regulator 1 downregulation and then promoted the acetylation and suppression of brain and muscle ARNT-like protein, thereby aggravating oxidative stress and apoptosis upon cerebral I/R injury. Our findings for the first time identify that USP29 upregulation during cerebral I/R may contribute to oxidative stress, neuronal apoptosis, and the progression of cerebral I/R injury and that inhibition of USP29 may help to develop novel therapeutic strategies to treat cerebral I/R injury.

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