CRE-mediated gene transcription in the peri-infarct area after focal cerebral ischemia in mice.
Cyclic AMP response element binding protein (CREB) is a transcription factor expressed constitutively primarily in neurons and is activated by phosphorylation at Ser(133) residue. CREB mediates expression of several neuroprotective proteins, including B-cell CLL/lymphoma 2 (BCL-2) and brain-derived neurotrophic factor (BDNF). Although phosphorylation of CREB after ischemia has been investigated extensively, CRE-mediated gene transcription after ischemia is not as well studied. We investigated temporal changes in CRE-mediated gene transcription in the cerebral cortex after focal ischemia in transgenic mice with a CRE-lacZ reporter gene. In the ischemic core, X-gal-positive cells, which reflected expression of the CRE-lacZ reporter gene, were observed rarely at any time point, though transient phosphorylation of CREB was detected. In contrast, the peri-infarct area showed a persistent increase in the number of X-gal-positive cells, of which more than half were positive for neuronal nuclei (NeuN). Our results suggest that CRE-mediated gene transcription, the pattern of which is not always consistent with that of CREB phosphorylation, occurs primarily in neurons in the peri-infarct area after focal cerebral ischemia and may be a neuroprotective response against ischemic insult.
Sugiura
Shiro
S
Division of Strokology, Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita, Japan. siro@medone.med.osaka-u.ac.jp
Kitagawa
Kazuo
K
Omura-Matsuoka
Emi
E
Sasaki
Tsutomu
T
Tanaka
Shigeru
S
Yagita
Yoshiki
Y
Matsushita
Kohji
K
Storm
Daniel R
DR
Hori
Masatsugu
M
D000818:Animals; D002545:Brain Ischemia / Q000473:pathology* / Q000503:physiopathology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics*; D015870:Gene Expression; D017930:Genes, Reporter; D007150:Immunohistochemistry; D007763:Lac Operon; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic; D001616:beta-Galactosidase / Q000378:metabolism
D017362:Cyclic AMP Response Element-Binding Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D001616:beta-Galactosidase