A hematopoietic growth factor, thrombopoietin, has a proapoptotic role in the brain.
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.
Ehrenreich
Hannelore
H
Max Planck Institute of Experimental Medicine, Georg-August University, 37075 Goettingen, Germany. ehrenreich@em.mpg.de
Hasselblatt
Martin
M
Knerlich
Friederike
F
von Ahsen
Nico
N
Jacob
Sonja
S
Sperling
Swetlana
S
Woldt
Helge
H
Vehmeyer
Katalin
K
Nave
Klaus-Armin
KA
Sirén
Anna-Leena
AL
D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000166:cytology* / Q000378:metabolism; D001923:Brain Chemistry; D004921:Erythropoietin / Q000502:physiology*; D005786:Gene Expression Regulation; D016298:Hematopoietic Cell Growth Factors / Q000502:physiology; D000860:Hypoxia / Q000378:metabolism; D020935:MAP Kinase Signaling System; D051379:Mice; D008810:Mice, Inbred C57BL; D009414:Nerve Growth Factors / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D016548:Prosencephalon / Q000737:chemistry / Q000166:cytology; D012249:Rhombencephalon / Q000737:chemistry / Q000166:cytology; D013926:Thrombopoietin / Q000502:physiology*
D016298:Hematopoietic Cell Growth Factors; D009414:Nerve Growth Factors; D004921:Erythropoietin; D013926:Thrombopoietin