Curcumin protects cortical neurons against oxygen and glucose deprivation/reoxygenation injury through flotillin-1 and extracellular signal-regulated kinase1/2 pathway

Na+–K+–Cl− cotransporter isoform 1 (NKCC1) and Na+/Ca2+ exchanger isoform 1 (NCX1) were expressed in cortical neurons. Three hours of oxygen and glucose deprivation (OGD) significantly increased expression of full-length NCX1 protein (∼116 kDa), which remained elevated during 1 to 21 h reoxygenation (REOX) and was accompanied with concurrent cleavage of NCX1. Na+/Ca2+ exchanger isoform 1 heterozygous (NCX1+/−) neurons with ∼50% less of NCX1 protein exhibited ∼64% reduction in NCX-mediated Ca2+ influx. Expression of NCX1 and NKCC1 proteins was reduced in double heterozygous (NCX1+/−/NKCC1+/−) neurons. NCX-mediated Ca2+ influx was nearly abolished in these neurons. Three-hour OGD and 21-h REOX caused ∼80% mortality rate in NCX1+/+ neurons and in NCX1+/− neurons. In contrast, NKCC1+/− neurons exhibited ∼45% less cell death. The lowest mortality rate was found in NCX1+/−/NKCC1+/− neurons (∼65% less neuronal death). The increased tolerance to ischemic damage was also observed in NCX1+/−/NKCC1+/− brains after transient cerebral ischemia. NCX1+/−/NKCC1+/− mice had a significantly reduced infarct volume at 24 and 72 h reperfusion. In conclusion, these data suggest that NKCC1 in conjunction with NCX1 plays a role in reperfusion-induced brain injury after ischemia.

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Neuroprotective and Anti-Apoptotic Effects of CSP-1103 in Primary Cortical Neurons Exposed to Oxygen and Glucose Deprivation

International Journal of Molecular Sciences ◽

10.3390/ijms18010184 ◽

2017 ◽

Vol 18 (1) ◽

pp. 184 ◽

Cited By ~ 3

Author(s):

Vanessa Porrini ◽

Ilenia Sarnico ◽

Marina Benarese ◽

Caterina Branca ◽

Mariana Mota ◽

...

Keyword(s):

Cortical Neurons ◽

Glucose Deprivation ◽

Primary Cortical Neurons ◽

Oxygen And Glucose Deprivation ◽

Apoptotic Effects

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Protective effects of XBP1 against oxygen and glucose deprivation/reoxygenation injury in rat primary hippocampal neurons

Neuroscience Letters ◽

10.1016/j.neulet.2012.04.053 ◽

2012 ◽

Vol 518 (1) ◽

pp. 45-48 ◽

Cited By ~ 18

Author(s):

Tatsuki Ibuki ◽

Yuki Yamasaki ◽

Hiroshi Mizuguchi ◽

Masahiro Sokabe

Keyword(s):

Hippocampal Neurons ◽

Glucose Deprivation ◽

Protective Effects ◽

Oxygen And Glucose Deprivation ◽

Primary Hippocampal Neurons ◽

Reoxygenation Injury

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ERK1/2-p90RSK-mediated Phosphorylation of Na+/H+ Exchanger Isoform 1

Journal of Biological Chemistry ◽

10.1074/jbc.m702373200 ◽

2007 ◽

Vol 282 (38) ◽

pp. 28274-28284 ◽

Cited By ~ 39

Author(s):

Jing Luo ◽

Douglas B. Kintner ◽

Gary E. Shull ◽

Dandan Sun

Keyword(s):

Nuclear Translocation ◽

Neuronal Damage ◽

Glucose Deprivation ◽

Mek Inhibitor ◽

Oxygen And Glucose Deprivation ◽

Genetic Ablation ◽

Extracellular Signal ◽

Nhe1 Activity ◽

Ribosomal S6 Kinase

The function and regulation of Na+/H+ exchanger isoform 1 (NHE1) following cerebral ischemia are not well understood. In this study, we demonstrate that extracellular signal-related kinases (ERK1/2) play a role in stimulation of neuronal NHE1 following in vitro ischemia. NHE1 activity was significantly increased during 10-60 min reoxygenation (REOX) after 2-h oxygen and glucose deprivation (OGD). OGD/REOX not only increased the Vmax for NHE1 but also shifted the Km toward decreased [H+]i. These changes in NHE1 kinetics were absent when MAPK/ERK kinase (MEK) was inhibited by the MEK inhibitor U0126. There were no changes in the levels of phosphorylated ERK1/2 (p-ERK1/2) after 2 h OGD. The p-ERK1/2 level was significantly increased during 10-60 min REOX, which was accompanied by nuclear translocation. U0126 abolished REOX-induced elevation and translocation of p-ERK1/2. We further examined the ERK/90-kDa ribosomal S6 kinase (p90RSK) signaling pathways. At 10 min REOX, phosphorylated NHE1 was increased with a concurrent elevation of phosphorylation of p90RSK, a known NHE1 kinase. Inhibition of MEK activity with U0126 abolished phosphorylation of both NHE1 and p90RSK. Moreover, neuroprotection was observed with U0126 or genetic ablation or pharmacological inhibition of NHE1 following OGD/REOX. Taken together, these results suggest that activation of ERK1/2-p90RSK pathways following in vitro ischemia phosphorylates NHE1 and increases its activity, which subsequently contributes to neuronal damage.

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