The Na+/H+ Exchanger-1 as a New Molecular Target in Stroke Interventions

Chanana, Vishal; Sun, Dandan; Ferrazzano, Peter

doi:10.5772/32126

Cited by 1 publication

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“…Human NHE1 protein consists of 815 amino acids with a calculated molecular weight of 85 kDa. However, because of the N-linked and O-linked glycosylation in its extracellular loop 1, the actual molecular weight of NHE1 can be varied from 85 to ~110 kDa in different cell types (19)(20)(21). Compared with NHE1 expression level in NSC, NHE1 protein was 9.8 ± 0.3 fold higher in GC#99, 15.6 ± 0.2 fold higher in GC#22 and 14.5 ± 1.2 fold in U87.…”

Section: Glioma Cells Express High Levels Of Nhe1 Proteinmentioning

confidence: 99%

Upregulation of NHE1 protein expression enables glioblastoma cells to escape TMZ-mediated toxicity via increased H⁺extrusion, cell migration and survival

Cong

Zhu

Shi

et al. 2014

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Sodium-hydrogen exchanger isoform 1 (NHE1) plays a role in survival and migration/invasion of several cancers and is an emerging new therapeutic target. However, the role of NHE1 in glioblastoma and the interaction of NHE1 expression and function in glioblastoma cells with cytotoxic temozolomide (TMZ) therapy remain unknown. In this study, we detected high levels of NHE1 protein only in primary human glioma cells (GC), glioma xenografts and glioblastoma, but not in human neural stem cells or astrocytes. GC exhibited an alkaline resting pH i (7.46 ± 0.04) maintained by robust NHE1-mediated H + extrusion. GC treatment with TMZ for 2-24 h triggered a transient decrease in pH i , which recovered by 48 h and correlated with concurrent upregulation of NHE1 protein expression. NHE1 protein was colocalized with ezrin at lamellipodia and probably involved in GC migration. The TMZ-treated GC exhibited increased migration and invasion, which was attenuated by addition of NHE1 inhibitor HOE-642. Most importantly, NHE1 inhibition prevented prosurvival extracellular signal-regulated kinase activation and accelerated TMZ-induced apoptosis. Taken together, our study provides the first evidence that GC upregulate NHE1 protein to maintain alkaline pH i . Combining TMZ therapy with NHE1 inhibition suppresses GC migration and invasion, and also augments TMZ-induced apoptosis. These findings strongly suggest that NHE1 is an important cytoprotective mechanism in GC and presents a new therapeutic strategy of combining NHE1 inhibition and TMZ chemotherapy.

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Section: Glioma Cells Express High Levels Of Nhe1 Proteinmentioning

confidence: 99%

Upregulation of NHE1 protein expression enables glioblastoma cells to escape TMZ-mediated toxicity via increased H⁺extrusion, cell migration and survival

Cong

Zhu

Shi

et al. 2014

CARCIN

Self Cite

View full text Add to dashboard Cite

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The Na+/H+ Exchanger-1 as a New Molecular Target in Stroke Interventions

Cited by 1 publication

References 75 publications

Upregulation of NHE1 protein expression enables glioblastoma cells to escape TMZ-mediated toxicity via increased H⁺extrusion, cell migration and survival

Upregulation of NHE1 protein expression enables glioblastoma cells to escape TMZ-mediated toxicity via increased H⁺extrusion, cell migration and survival

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The Na+/H+ Exchanger-1 as a New Molecular Target in Stroke Interventions

Cited by 1 publication

References 75 publications

Upregulation of NHE1 protein expression enables glioblastoma cells to escape TMZ-mediated toxicity via increased H+extrusion, cell migration and survival

Upregulation of NHE1 protein expression enables glioblastoma cells to escape TMZ-mediated toxicity via increased H+extrusion, cell migration and survival

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Upregulation of NHE1 protein expression enables glioblastoma cells to escape TMZ-mediated toxicity via increased H⁺extrusion, cell migration and survival

Upregulation of NHE1 protein expression enables glioblastoma cells to escape TMZ-mediated toxicity via increased H⁺extrusion, cell migration and survival