Phosphorylation of Cyclic Adenosine Monophosphate Response Element Binding Protein in Oligodendrocytes in the Corpus Callosum after Focal Cerebral Ischemia in the Rat
Phosphorylation of Cyclic Adenosine Monophosphate Response Element Binding Protein in Oligodendrocytes in the Corpus Callosum after Focal Cerebral Ischemia in the Rat
复制标题
大鼠局灶性脑缺血后胼胝体少突胶质细胞环磷酸腺苷反应元件结合蛋白的磷酸化
DOI：
10.1097/00004647-200110000-00006
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发表时间：
2001
影响因子：
6.3
通讯作者：
Y. Fukuuchi
中科院分区：
文献类型：
--
作者：
Kortaro Tanaka;S. Nogawa;D. Ito;Shigeaki Suzuki;T. Dembo;A. Kosakai;Y. Fukuuchi
用免疫组织化学方法检测局灶性脑缺血90分钟后不同时间点大鼠脑胼胝体中环腺苷单磷酸（AMP）反应元件结合蛋白（CREB）的磷酸化水平。采用腔内缝合法闭塞大脑中动脉（MCA）致局灶性缺血。假动物实验表明，许多少突胶质细胞（OLGs）组成性地表达未磷酸化的CREB。在MCA闭塞（MCAO）期间，用14c -碘安替比林方法测量的胼胝体内侧和外侧区域局部脑血流量（lCBF）分别从44.2±15.4 （mL 100 g−1 min−1）降至18.4±3.8和53.9±14.4降至4.8±4.5。MCAO发布后，各地区lCBF恢复到控制水平。胼胝体内侧区磷酸化的creb阳性OLGs在再循环3.5小时时明显增加，直到再循环2周后逐渐下降。在OLGs中，CREB磷酸化的激活伴随着抗凋亡蛋白bcl-2的表达，甲酰紫染色正常，TUNEL（末端脱氧核苷酸转移酶介导的脱氧尿苷三磷酸镍端标记）染色阴性。抗髓鞘碱性蛋白（MBP）抗体和抗髓鞘相关糖蛋白（MAG）抗体免疫染色检测胼胝体内侧区髓鞘形成正常。胼胝体外侧区磷酸化的creb阳性OLGs在再循环3.5小时时出现了显著但短暂的增加，随后在随后的再循环期间迅速下降。bcl-2在该区域的表达被抑制，脱髓鞘明显。这些发现表明，通过CREB磷酸化进行的信号转导可能与脑缺血后OLGs的存活和胼胝体髓鞘形成的维持密切相关。
Phosphorylation of cyclic adenosine monophosphate (AMP) response element binding protein (CREB) was examined immunohistochemically in the corpus callosum of the rat brain at various time points after 90-minute focal cerebral ischemia. Focal ischemia was induced by occlusion of the middle cerebral artery (MCA) using the intraluminal suture method. Sham animals showed that numerous oligodendrocytes (OLGs) constitutively express unphosphorylated CREB. Local cerebral blood flow (lCBF) measured by the14 C-iodoantipyrine method was reduced from 44.2 ± 15.4 (mL 100 g−1 min−1) to 18.4 ± 3.8 and from 53.9 ± 14.4 to 4.8 ± 4.5 in the medial and the lateral regions of the corpus callosum, respectively, during MCA occlusion (MCAO). After release of the MCAO, lCBF recovered to the control level in each region. The medial region of the corpus callosum showed a marked increase in phosphorylated CREB-positive OLGs at 3.5 hours of recirculation, and it remained increased until 2 weeks of recirculation as it gradually declined. The activation of CREB phosphorylation in the OLGs was accompanied by expression of antiapoptotic protein bcl-2, normal staining with cresyl violet, and negative TUNEL (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling) staining. Myelination detected by immunostaining with anti-myelin basic protein (MBP) antibody and anti-myelin associated glycoprotein (MAG) antibody remained normal in the medial region of the corpus callosum. The lateral region of the corpus callosum showed a significant but only transient increase in phosphorylated CREB-positive OLGs at 3.5 hours of recirculation, which was followed by a rapid decrease during the subsequent recirculation period. Expression of bcl-2 was suppressed in this region, and demyelination became apparent. These findings suggest that signal transduction through CREB phosphorylation may be closely associated with survival of OLGs and maintenance of myelination in the corpus callosum after cerebral ischemia.
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影响因子：
56.9
作者：
GINTY, DD;KORNHAUSER, JM;GREENBERG, ME
通讯作者：
GREENBERG, ME
影响因子：
56.9
作者：
Bonni, A;Brunet, A;Greenberg, ME
通讯作者：
Greenberg, ME
影响因子：
56.9
作者：
Riccio, A;Ahn, S;Ginty, DD
通讯作者：
Ginty, DD
影响因子：
8.3
作者：
Pantoni, L;Garcia, JH;Gutierrez, JA
通讯作者：
Gutierrez, JA