Major role of the PI3K/Akt pathway in ischemic tolerance induced by sublethal oxygen-glucose deprivation in cortical neurons in vitro

2011 ◽  
Vol 34 (6) ◽  
pp. 1023-1034 ◽  
Author(s):  
Mohammad Iqbal Hossain Bhuiyan ◽  
Seo Yun Jung ◽  
Hyoung Ja Kim ◽  
Yong Sup Lee ◽  
Changbae Jin
Keyword(s):  
Cortical Neurons ◽  
Glucose Deprivation ◽  
Ischemic Tolerance ◽  
Akt Pathway ◽  
Oxygen Glucose Deprivation

scholarly journals Role of long noncoding RNA MEG3/miR-378/GRB2 axis in neuronal autophagy and neurological functional impairment in ischemic stroke

2020 ◽  
Vol 295 (41) ◽  
pp. 14125-14139 ◽  
Author(s):  
Hong-Cheng Luo ◽  
Ting-Zhuang Yi ◽  
Fu-Gao Huang ◽  
Ying Wei ◽  
Xiao-Peng Luo ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Functional Impairment ◽  
Molecular Mechanisms ◽  
Glucose Deprivation ◽  
Oxygen Glucose Deprivation ◽  
Neuronal Autophagy

Autophagy has been shown to maintain neural system homeostasis during stroke. However, the molecular mechanisms underlying neuronal autophagy in ischemic stroke remain poorly understood. This study aims to investigate the regulatory mechanisms of the pathway consisting of MEG3 (maternally expressed gene 3), microRNA-378 (miR-378), and GRB2 (growth factor receptor-bound protein 2) in neuronal autophagy and neurological functional impairment in ischemic stroke. A mouse model of the middle cerebral artery occluded–induced ischemic stroke and an in vitro model of oxygen-glucose deprivation–induced neuronal injury were developed. To understand the role of the MEG3/miR-378/GRB2 axis in the neuronal regulation, the expression of proteins associated with autophagy in neurons was measured by Western blotting analysis, and neuron death was evaluated using a lactate dehydrogenase leakage rate test. First, it was found that the GRB2 gene, up-regulated in middle cerebral artery occluded–operated mice and oxygen-glucose deprivation–exposed neurons, was a target gene of miR-378. Next, miR-378 inhibited neuronal loss and neurological functional impairment in mice, as well as neuronal autophagy and neuronal death by silencing of GRB2. Confirmatory in vitro experiments showed that MEG3 could specifically bind to miR-378 and subsequently up-regulate the expression of GRB2, which in turn suppressed the activation of Akt/mTOR pathway. Taken together, these findings suggested that miR-378 might protect against neuronal autophagy and neurological functional impairment and proposed that a MEG3/miR-378/GRB2 regulatory axis contributed to better understanding of the pathophysiology of ischemic stroke.

scholarly journals LACTIC ACIDOSIS REDUCES INJURY OF MOUSE CORTICAL NEURONS DUE TO OXYGEN-GLUCOSE DEPRIVATION IN VITRO

1990 ◽  
Vol 70 (Supplement) ◽  
pp. S125 ◽  
Author(s):  
R. G. Giffard ◽  
H. Monyer ◽  
M. P. Goldberg ◽  
D. W. Choi
Keyword(s):  
Lactic Acidosis ◽  
Cortical Neurons ◽  
Glucose Deprivation ◽  
Oxygen Glucose Deprivation

scholarly journals Angiotensin II protects cortical neurons against oxygen-glucose deprivation-induced injury in vitro

2013 ◽  
Vol 2 (1) ◽  
pp. 112-116 ◽  
Author(s):  
MINGTAN TANG ◽  
LI ZHAO ◽  
YANQING CHEN ◽  
LIXIANG WANG ◽  
XIUMEI ZHANG
Keyword(s):  
Angiotensin Ii ◽  
Cortical Neurons ◽  
Glucose Deprivation ◽  
Oxygen Glucose Deprivation

scholarly journals Role of Intracellular Calcium Stores in Cell Death from Oxygen–Glucose Deprivation in a Neuronal Cell Line

2002 ◽  
Vol 22 (2) ◽  
pp. 206-214 ◽  
Author(s):  
Chen Wang ◽  
Henry N. Nguyen ◽  
Jamie L. Maguire ◽  
David C. Perry
Keyword(s):  
Calcium Homeostasis ◽  
Drug Exposure ◽  
Neuronal Cell ◽  
Glucose Deprivation ◽  
Recovery Phase ◽  
Oxygen Glucose Deprivation ◽  
Calcium Stores ◽  
Human Neuroblastoma

To determine the role of calcium homeostasis in ischemic neuronal death, the authors used an in vitro model of oxygen–glucose deprivation in neuronal cell lines. Exposure of human neuroblastoma SH-SY5Y cells to 10- to 16-hour oxygen–glucose deprivation decreased viability to 50% or less, and longer exposure times killed almost all cells. The death following 10- to 16-hour oxygen–glucose deprivation was not manifested until 24 to 72 hours after exposure. Deprivation of both glucose and oxygen together was required for expression of toxicity at these exposure times. Dantrolene, which blocks the release of endoplasmic reticulum Ca2+ stores, partially protected SH-SY5Y cells from oxygen–glucose deprivation toxicity. The addition of dantrolene during the deprivation phase alone produced the maximal drug effect; no further protection was obtained by continued drug exposure during the recovery phase. Prevention of Ca2+ influx by chelation or channel blockade or the chelation of cytosolic Ca2+ did not inhibit oxygen-glucose deprivation toxicity. In contrast, increasing extracellular Ca2+ or stimulating Ca2+ influx did inhibit toxicity. Calcium measurements with fura-2 acetoxymethylester revealed that oxygen–glucose deprivation caused a significant reduction in thapsigargin-releasable endoplasmic reticular stores of Ca2+. These studies suggest that an important component of the neuronal toxicity in cerebral ischemia is due to disruption of calcium homeostasis, particularly to the depletion of intracellular Ca2+ stores.

Sign in / Sign up

Export Citation Format

Share Document