A hematopoietic growth factor, thrombopoietin, has a proapoptotic role in the brain

被引：76

作者：

Ehrenreich, H ^{[1
]}

Hasselblatt, M

Knerlich, F

von Ahsen, N

Jacob, S

Sperling, S

Woldt, H

Vehmeyer, K

Nave, KA

Sirén, AL

机构：

[1] Univ Gottingen, Max Planck Inst Expt Med, D-37075 Gottingen, Germany

[2] Univ Gottingen, Dept Clin Chem, D-37075 Gottingen, Germany

[3] Univ Gottingen, Dept Hematol & Oncol, D-37075 Gottingen, Germany

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2005年 / 102卷 / 03期

关键词：

astrocytes; erythropoietin; neurons; differentiation; development;

D O I：

10.1073/pnas.0406008102

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Central nervous and hematopoietic systems share developmental features. We report that thrombopoietin (TPO), a stimulator of platelet formation, acts in the brain as a counterpart of erythropoietin (EPO), a hematopoietic growth factor with neuroprotective properties. TPO is most prominent in postnatal brain, whereas EPO is abundant in embryonic brain and decreases postnatally. Upon hypoxia, EPO and its receptor are rapidly reexpressed, whereas neuronal TPO and its receptor are down-regulated. Unexpectedly, TPO is strongly proapoptotic in the brain, causing death of newly generated neurons through the Ras-extracellular signal-regulated kinase 1/2 pathway. This effect is not only inhibited by EPO but also by neurotrophins. We suggest that the proapoptotic function of TPO helps to select for neurons that have acquired target-derived neurotrophic support.

引用

页码：862 / 867

页数：6

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