PMID- 19598250
OWN - NLM
STAT- MEDLINE
DCOM- 20100105
LR  - 20131121
IS  - 1097-4547 (Electronic)
IS  - 0360-4012 (Linking)
VI  - 87
IP  - 16
DP  - 2009 Dec
TI  - Tissue kallikrein alleviates glutamate-induced neurotoxicity by activating ERK1.
PG  - 3576-90
LID - 10.1002/jnr.22151 [doi]
AB  - Glutamate-induced neurotoxicity consequent to N-methyl-D-aspartic acid (NMDA) and 
      2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl) propionic acid (AMPA) receptor 
      activation underlies the pathogenesis of a wide range of central nervous system 
      disorders, including brain ischemia. Prevention of ischemia/reperfusion 
      (I/R)-induced neuronal injury has long been regarded as an effective therapeutic 
      strategy for ischemia. Human tissue kallikrein (TK) gene transfer has been shown 
      to protect neurons against cerebral I/R-induced apoptosis and oxidative stress, 
      via activation of the brandykinin B2 receptor (B2R). However, little is known 
      about the role of TK on glutamate-induced neurotoxicity. Here we report that 
      pretreatment of cultured cortical neurons with TK largely prevented 
      glutamate-induced morphological changes and cell death. We found that TK 
      pretreatment alleviated glutamate-induced oxidative stress by inhibiting neuronal 
      nitric oxide synthase (nNOS) activity, thereby reducing the generation of nitric 
      oxide (NO) and reactive oxygen species (ROS). Blockage of NMDA and AMPA receptors 
      by their specific antagonists MK801 and CNQX had effects similar to those of TK 
      administration. Furthermore, we found that the extracellular signal-regulated 
      kinase 1/2 cascade (ERK1/2), particularly ERK1, and nuclear factor-kappaB 
      (NF-kappaB) were involved in TK neuroprotection against glutamate-induced 
      neurotoxicity. TK pretreatment activated ERK1 and NF-kappaB, leading to enhanced 
      expression of brain-derived neurotrophic factor (BDNF) mRNA and antiapoptotic 
      gene Bcl-2 protein. Collectively, these findings demonstrate that TK attenuates 
      glutamate-induced apoptosis through an intracellular signaling pathway including 
      activation of B2R, ERK1/2, and NF-kappaB and up-regulation of BDNF and Bcl-2 
      expression. Thus, TK represents a promising therapeutic strategy for ischemic 
      stroke.
CI  - Copyright 2009 Wiley-Liss, Inc.
FAU - Liu, Ling
AU  - Liu L
AD  - Department of Neurology, Jinling Hospital, Nanjing University School of Medicine, 
      Nanjing, People's Republic of China.
FAU - Zhang, Renliang
AU  - Zhang R
FAU - Liu, Kui
AU  - Liu K
FAU - Zhou, Houguang
AU  - Zhou H
FAU - Tang, Yuping
AU  - Tang Y
FAU - Su, Jinjin
AU  - Su J
FAU - Yu, Xiaoyan
AU  - Yu X
FAU - Yang, Xuelian
AU  - Yang X
FAU - Tang, Min
AU  - Tang M
FAU - Dong, Qiang
AU  - Dong Q
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Neurosci Res
JT  - Journal of neuroscience research
JID - 7600111
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Excitatory Amino Acid Antagonists)
RN  - 0 (NF-kappa B)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Receptors, AMPA)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - 6LR8C1B66Q (Dizocilpine Maleate)
RN  - 6OTE87SCCW (6-Cyano-7-nitroquinoxaline-2,3-dione)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type I)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - EC 3.4.21.35 (Tissue Kallikreins)
SB  - IM
MH  - 6-Cyano-7-nitroquinoxaline-2,3-dione/pharmacology
MH  - Analysis of Variance
MH  - Animals
MH  - Apoptosis/*drug effects
MH  - Blotting, Western
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Cells, Cultured
MH  - Cerebral Cortex/cytology/drug effects/metabolism
MH  - Cytoprotection
MH  - Dizocilpine Maleate/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Excitatory Amino Acid Antagonists/pharmacology
MH  - Glutamic Acid/*toxicity
MH  - Immunohistochemistry
MH  - In Situ Nick-End Labeling
MH  - Mitogen-Activated Protein Kinase 3/*metabolism
MH  - NF-kappa B/metabolism
MH  - Neurons/*drug effects/metabolism/pathology
MH  - Nitric Oxide/metabolism
MH  - Nitric Oxide Synthase Type I/metabolism
MH  - Oxidative Stress/drug effects
MH  - Proto-Oncogene Proteins c-bcl-2/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reactive Oxygen Species/metabolism
MH  - Receptors, AMPA/metabolism
MH  - Receptors, N-Methyl-D-Aspartate/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Signal Transduction/drug effects
MH  - Tissue Kallikreins/administration & dosage/*metabolism
MH  - Up-Regulation/drug effects
EDAT- 2009/07/15 09:00
MHDA- 2010/01/06 06:00
CRDT- 2009/07/15 09:00
PHST- 2009/07/15 09:00 [entrez]
PHST- 2009/07/15 09:00 [pubmed]
PHST- 2010/01/06 06:00 [medline]
AID - 10.1002/jnr.22151 [doi]
PST - ppublish
SO  - J Neurosci Res. 2009 Dec;87(16):3576-90. doi: 10.1002/jnr.22151.