Npas4, a novel helix-loop-helix PAS domain protein, is regulated in response to cerebral ischemia
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Npas4, a novel helix-loop-helix PAS domain protein, is regulated in response to cerebral ischemia. / Shamloo, Mehrdad; Soriano, Liza; von Schack, David; Rickhag, Karl Mattias; Chin, Daniel J; Gonzalez-Zulueta, Mirella; Gido, Gunilla; Urfer, Roman; Wieloch, Tadeusz; Nikolich, Karoly.
In: European Journal of Neuroscience, Vol. 24, No. 10, 11.2006, p. 2705-20.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Npas4, a novel helix-loop-helix PAS domain protein, is regulated in response to cerebral ischemia
AU - Shamloo, Mehrdad
AU - Soriano, Liza
AU - von Schack, David
AU - Rickhag, Karl Mattias
AU - Chin, Daniel J
AU - Gonzalez-Zulueta, Mirella
AU - Gido, Gunilla
AU - Urfer, Roman
AU - Wieloch, Tadeusz
AU - Nikolich, Karoly
PY - 2006/11
Y1 - 2006/11
N2 - Basic helix-loop-helix PAS domain proteins form a growing family of transcription factors. These proteins are involved in the process of adaptation to cellular stresses and environmental factors such as a change in oxygen concentration. We describe the identification and characterization of a recently cloned PAS domain protein termed Npas4 in ischemic rat brain. Using gene expression profiling following middle cerebral artery occlusion, we showed that the Npas4 mRNA is differentially expressed in ischemic tissue. The full-length gene was cloned from rat brain and its spatial and temporal expression characterized with in situ hybridization and Northern blotting. The Npas4 mRNA is specifically expressed in the brain and is highly up-regulated in ischemic tissues following both focal and global cerebral ischemic insults. Immunohistochemistry revealed a strong expression in the limbic system and thalamus, as well as in layers 3 and 5 in the cortex of the unchallenged brain. When overexpressed in HEK 293 cells, Npas4 appears as a protein of approximately 100 kDa. In brain samples, however, in addition to the 100 kDa band a specific 200 kDa immunoreactive band was also detected. Ischemic challenge lead to a decrease in the 200 kDa form and a simultaneous increase in the 100 kDa immunoreactivity. This could indicate a novel regulatory mechanism for activation and/or deactivation of this protein in response to ischemic brain injury.
AB - Basic helix-loop-helix PAS domain proteins form a growing family of transcription factors. These proteins are involved in the process of adaptation to cellular stresses and environmental factors such as a change in oxygen concentration. We describe the identification and characterization of a recently cloned PAS domain protein termed Npas4 in ischemic rat brain. Using gene expression profiling following middle cerebral artery occlusion, we showed that the Npas4 mRNA is differentially expressed in ischemic tissue. The full-length gene was cloned from rat brain and its spatial and temporal expression characterized with in situ hybridization and Northern blotting. The Npas4 mRNA is specifically expressed in the brain and is highly up-regulated in ischemic tissues following both focal and global cerebral ischemic insults. Immunohistochemistry revealed a strong expression in the limbic system and thalamus, as well as in layers 3 and 5 in the cortex of the unchallenged brain. When overexpressed in HEK 293 cells, Npas4 appears as a protein of approximately 100 kDa. In brain samples, however, in addition to the 100 kDa band a specific 200 kDa immunoreactive band was also detected. Ischemic challenge lead to a decrease in the 200 kDa form and a simultaneous increase in the 100 kDa immunoreactivity. This could indicate a novel regulatory mechanism for activation and/or deactivation of this protein in response to ischemic brain injury.
KW - Animals
KW - Basic Helix-Loop-Helix Transcription Factors
KW - Blotting, Northern
KW - Blotting, Western
KW - Brain
KW - Cells, Cultured
KW - Embryo, Mammalian
KW - Gene Expression Regulation
KW - Helix-Loop-Helix Motifs
KW - Immunohistochemistry
KW - In Situ Hybridization
KW - Infarction, Middle Cerebral Artery
KW - Male
KW - Nerve Tissue Proteins
KW - Neurons
KW - RNA, Messenger
KW - Rats
KW - Rats, Wistar
KW - Reverse Transcriptase Polymerase Chain Reaction
KW - Subcellular Fractions
KW - Synaptophysin
KW - Time Factors
U2 - 10.1111/j.1460-9568.2006.05172.x
DO - 10.1111/j.1460-9568.2006.05172.x
M3 - Journal article
C2 - 17156197
VL - 24
SP - 2705
EP - 2720
JO - European Journal of Neuroscience
JF - European Journal of Neuroscience
SN - 0953-816X
IS - 10
ER -
ID: 132931360