Mulberroside a protects against ischemic impairment in primary culture of rat cortical neurons after oxygen-glucose deprivation followed by reperfusion

2014 ◽  
Vol 92 (7) ◽  
pp. 944-954 ◽  
Author(s):  
Cai-Ping Wang ◽  
Lu-Zhong Zhang ◽  
Gui-Cai Li ◽  
Yun-wei Shi ◽  
Jian-Long Li ◽  
...  
Keyword(s):  
Primary Culture ◽  
Cortical Neurons ◽  
Glucose Deprivation ◽  
Oxygen Glucose Deprivation ◽  
Rat Cortical Neurons ◽  
Mulberroside A

scholarly journals Neuroprotective effects of orientin on oxygen-glucose deprivation/reperfusion-induced cell injury in primary culture of rat cortical neurons

2017 ◽  
Vol 243 (1) ◽  
pp. 78-86 ◽  
Author(s):  
Tian Tian ◽  
Junan Zeng ◽  
Guangyu Zhao ◽  
Wenjing Zhao ◽  
Songyi Gao ◽  
...  
Keyword(s):  
Primary Culture ◽  
Cortical Neurons ◽  
Caspase 3 ◽  
Cell Injury ◽  
Antioxidant Properties ◽  
Glucose Deprivation ◽  
Oxygen Glucose Deprivation ◽  
Ros Generation ◽  
Neuroprotective Effects ◽  
Rat Cortical Neurons

Orientin (luteolin-8-C-glucoside) is a phenolic compound found abundantly in millet, juice, and peel of passion fruit and has been shown to have antioxidant properties. In the present study, we explored the effects of orientin on oxygen-glucose deprivation/reperfusion (OGD/RP)-induced cell injury in primary culture of rat cortical neurons using an in vitro model of neonatal ischemic brain injury. The reduced cell viability and elevated lactate dehydrogenase leakage were observed after OGD/RP exposure, which were then reversed by orientin (10, 20, and 30 µM) pretreatment in a dose-dependent manner. Additionally, OGD/RP treatment resulted in significant oxidative stress, accompanied by enhanced intracellular reactive oxygen species (ROS) generation, and obvious depletion in the activities of intracellular Mn-superoxide dismutase, catalase, and glutathione peroxidase antioxidases. However, these effects were dose dependently restored by orientin pretreatment. We also found that orientin pretreatment dose dependently suppressed [Ca2+]i increase and mitochondrial membrane potential dissipation caused by OGD/RP in primary culture of rat cortical neurons. Western blot analysis showed that OGD/RP exposure induced a distinct decrease of Bcl-2 protein and a marked elevation of Bax, caspase-3, and cleaved caspase-3 proteins; whereas these effects were dose dependently reversed by orientin incubation. Both the caspase-3 activity and the apoptosis rate were increased under OGD/RP treatment, but was then dose dependently down-regulated by orientin (10, 20, and 30 µM) incubation. Moreover, orientin pretreatment dose dependently inhibited OGD/RP-induced phosphorylation of JNK and ERK1/2. Notably, JNK inhibitor SP600125 and ERK1/2 inhibitor PD98059 also dramatically attenuated OGD/RP-induced cell viability loss and ROS generation, and further, orientin failed to protect cortical neurons with the interference of JNK activator anisomycin or ERK1/2 activator FGF-2. Taken together, these results demonstrated that orientin has significant neuroprotective effects against OGD/RP-induced cell injury via JNK and ERK1/2 signaling pathways in primary culture of rat cortical neurons. Impact statement Orientin has been used in traditional eastern medicine and reported to possess antioxidant properties. However, the effects of orientin on neonatal ischemic brain injury and the underlying mechanisms involved have not been studied. Our results showed that orientin exerts significant neuroprotective effects on cell injury caused by oxygen-glucose deprivation/reperfusion via the JNK and ERK1/2 signaling pathways in primary culture of rat cortical neurons, implying the potential therapeutic application of orientin via the suppression of oxidative stress and cell apoptosis. This research suggested that orientin may be used as a therapeutic and preventive option for newborn cerebral ischemia/reperfusion injury.

scholarly journals Proteolysis of Oxidized Proteins after Oxygen–Glucose Deprivation in Rat Cortical Neurons is Mediated by the Proteasome

2001 ◽  
Vol 21 (9) ◽  
pp. 1090-1096 ◽  
Author(s):  
Markus Weih ◽  
Marion Schmitt ◽  
Janette Gieche ◽  
Christoph Harms ◽  
Karsten Ruscher ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Cortical Neurons ◽  
Oxidative Injury ◽  
Glucose Deprivation ◽  
Cellular Damage ◽  
Protein Carbonyls ◽  
Oxygen Glucose Deprivation ◽  
Radical Scavenger ◽  
Oxidized Proteins ◽  
Rat Cortical Neurons

Oxidative injury contributes to cellular damage during and after cerebral ischemia. However, the downstream catabolic pathways of damaged cellular components in neurons are largely unknown. In the current study, the authors examined the formation of oxidized proteins and their active degradation by the proteasome. In near-pure rat primary cortical neurons, it was found that protein-bound carbonyls as markers for oxidized proteins are increased after oxygen-glucose deprivation (OGD). During and after OGD, degradation of proteins metabolically radiolabeled before OGD increases two-to threefold compared with the normal protein turnover. Proteolysis after reoxygenation was attenuated by the presence of dimethylthiourea, a radical scavenger, and was blocked by lactacystin, a specific proteasome inhibitor. Lactacystin also increased the amount of protein carbonyls formed. In contrast, the activity of the proteasome complex itself after OGD was not different from sham-washed controls. The authors suggest that oxygen-glucose deprivation increases free radicals, which, in turn, oxidize proteins that are recognized and actively degraded by the proteasome complex. This protease itself is relatively resistant against oxidative injury. The authors conclude that the proteasome may be an active part of the cellular defense system against oxidative stress after cerebral ischemia.

Sign in / Sign up

Export Citation Format

Share Document