Activation of death-associated protein kinase in human peritumoral tissue: A potential therapeutic target

Xiang Gao, Haiyan Wang, Karen Pollok, Jinhui Chen, Aaron Cohen-Gadol

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

To further understand the molecular mechanisms of N-methyl-D-aspartate receptor 2B (NR2B) phosphorylation and its contribution to glioma-related seizures, we investigated the expression of death-associated protein kinase-1 (DAPK1), which is a kinase known to phosphorylate NR2B at S1303 in glioma and peritumoral tissue. The molecular mechanisms leading to glioma-associated seizures are poorly understood. We recently discovered that NR2B is phosphorylated at S1303 in glioma peritumoral tissue. NR2B is an excitatory glutamate receptor, suggesting that glutamate released from glioma tumor cells may excite the neurons in the peritumoral tissue and contribute to glioma-associated epileptogenesis. DAPK1 levels were assessed in an intracranial mouse model of human glioma and in primary patient peritumoral and glioma tissues using immunohistochemistry. DAPK1 is highly expressed in the peritumoral region, but is poorly expressed in glioma tissues in both a mouse model of human glioma and in the primary patient glioma. In our previous report, we found that NR2B is also highly phosphorylated in the same region. Upregulation of DAPK1 in the peritumoral tissues suggests that DAPK1 can phosphorylate NR2B, increase its excitability, lead to glioma-induced seizures, and could potentially be an important therapeutic target. Furthermore, the xenograft model offers an opportunity to develop and test therapeutic approaches that can block DAPK1 activity in vivo.

Original languageEnglish
Article number6063
Pages (from-to)1655-1660
Number of pages6
JournalJournal of Clinical Neuroscience
Volume22
Issue number10
DOIs
StatePublished - Oct 1 2015

Fingerprint

Death-Associated Protein Kinases
Glioma
Therapeutics
Seizures
Glutamate Receptors
Heterografts

Keywords

  • Death associated protein kinase 1
  • Glioblastoma multiforme
  • Peritumoral seizures

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology
  • Physiology (medical)

Cite this

Activation of death-associated protein kinase in human peritumoral tissue : A potential therapeutic target. / Gao, Xiang; Wang, Haiyan; Pollok, Karen; Chen, Jinhui; Cohen-Gadol, Aaron.

In: Journal of Clinical Neuroscience, Vol. 22, No. 10, 6063, 01.10.2015, p. 1655-1660.

Research output: Contribution to journalArticle

@article{8ed5b249a0d64c709204754c2df9f5bd,
title = "Activation of death-associated protein kinase in human peritumoral tissue: A potential therapeutic target",
abstract = "To further understand the molecular mechanisms of N-methyl-D-aspartate receptor 2B (NR2B) phosphorylation and its contribution to glioma-related seizures, we investigated the expression of death-associated protein kinase-1 (DAPK1), which is a kinase known to phosphorylate NR2B at S1303 in glioma and peritumoral tissue. The molecular mechanisms leading to glioma-associated seizures are poorly understood. We recently discovered that NR2B is phosphorylated at S1303 in glioma peritumoral tissue. NR2B is an excitatory glutamate receptor, suggesting that glutamate released from glioma tumor cells may excite the neurons in the peritumoral tissue and contribute to glioma-associated epileptogenesis. DAPK1 levels were assessed in an intracranial mouse model of human glioma and in primary patient peritumoral and glioma tissues using immunohistochemistry. DAPK1 is highly expressed in the peritumoral region, but is poorly expressed in glioma tissues in both a mouse model of human glioma and in the primary patient glioma. In our previous report, we found that NR2B is also highly phosphorylated in the same region. Upregulation of DAPK1 in the peritumoral tissues suggests that DAPK1 can phosphorylate NR2B, increase its excitability, lead to glioma-induced seizures, and could potentially be an important therapeutic target. Furthermore, the xenograft model offers an opportunity to develop and test therapeutic approaches that can block DAPK1 activity in vivo.",
keywords = "Death associated protein kinase 1, Glioblastoma multiforme, Peritumoral seizures",
author = "Xiang Gao and Haiyan Wang and Karen Pollok and Jinhui Chen and Aaron Cohen-Gadol",
year = "2015",
month = "10",
day = "1",
doi = "10.1016/j.jocn.2015.03.044",
language = "English",
volume = "22",
pages = "1655--1660",
journal = "Journal of Clinical Neuroscience",
issn = "0967-5868",
publisher = "Churchill Livingstone",
number = "10",

}

TY - JOUR

T1 - Activation of death-associated protein kinase in human peritumoral tissue

T2 - A potential therapeutic target

AU - Gao, Xiang

AU - Wang, Haiyan

AU - Pollok, Karen

AU - Chen, Jinhui

AU - Cohen-Gadol, Aaron

PY - 2015/10/1

Y1 - 2015/10/1

N2 - To further understand the molecular mechanisms of N-methyl-D-aspartate receptor 2B (NR2B) phosphorylation and its contribution to glioma-related seizures, we investigated the expression of death-associated protein kinase-1 (DAPK1), which is a kinase known to phosphorylate NR2B at S1303 in glioma and peritumoral tissue. The molecular mechanisms leading to glioma-associated seizures are poorly understood. We recently discovered that NR2B is phosphorylated at S1303 in glioma peritumoral tissue. NR2B is an excitatory glutamate receptor, suggesting that glutamate released from glioma tumor cells may excite the neurons in the peritumoral tissue and contribute to glioma-associated epileptogenesis. DAPK1 levels were assessed in an intracranial mouse model of human glioma and in primary patient peritumoral and glioma tissues using immunohistochemistry. DAPK1 is highly expressed in the peritumoral region, but is poorly expressed in glioma tissues in both a mouse model of human glioma and in the primary patient glioma. In our previous report, we found that NR2B is also highly phosphorylated in the same region. Upregulation of DAPK1 in the peritumoral tissues suggests that DAPK1 can phosphorylate NR2B, increase its excitability, lead to glioma-induced seizures, and could potentially be an important therapeutic target. Furthermore, the xenograft model offers an opportunity to develop and test therapeutic approaches that can block DAPK1 activity in vivo.

AB - To further understand the molecular mechanisms of N-methyl-D-aspartate receptor 2B (NR2B) phosphorylation and its contribution to glioma-related seizures, we investigated the expression of death-associated protein kinase-1 (DAPK1), which is a kinase known to phosphorylate NR2B at S1303 in glioma and peritumoral tissue. The molecular mechanisms leading to glioma-associated seizures are poorly understood. We recently discovered that NR2B is phosphorylated at S1303 in glioma peritumoral tissue. NR2B is an excitatory glutamate receptor, suggesting that glutamate released from glioma tumor cells may excite the neurons in the peritumoral tissue and contribute to glioma-associated epileptogenesis. DAPK1 levels were assessed in an intracranial mouse model of human glioma and in primary patient peritumoral and glioma tissues using immunohistochemistry. DAPK1 is highly expressed in the peritumoral region, but is poorly expressed in glioma tissues in both a mouse model of human glioma and in the primary patient glioma. In our previous report, we found that NR2B is also highly phosphorylated in the same region. Upregulation of DAPK1 in the peritumoral tissues suggests that DAPK1 can phosphorylate NR2B, increase its excitability, lead to glioma-induced seizures, and could potentially be an important therapeutic target. Furthermore, the xenograft model offers an opportunity to develop and test therapeutic approaches that can block DAPK1 activity in vivo.

KW - Death associated protein kinase 1

KW - Glioblastoma multiforme

KW - Peritumoral seizures

UR - http://www.scopus.com/inward/record.url?scp=84941167068&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84941167068&partnerID=8YFLogxK

U2 - 10.1016/j.jocn.2015.03.044

DO - 10.1016/j.jocn.2015.03.044

M3 - Article

C2 - 26165472

AN - SCOPUS:84941167068

VL - 22

SP - 1655

EP - 1660

JO - Journal of Clinical Neuroscience

JF - Journal of Clinical Neuroscience

SN - 0967-5868

IS - 10

M1 - 6063

ER -