Derivatives of erythropoietin that are tissue protective but not erythropoietic

被引：678

作者：

Leist, M

Ghezzi, P

Grasso, G

Bianchi, R

Villa, P

Fratelli, M

Savino, C

Bianchi, M

Nielsen, J

Gerwien, J

Kallunki, P

Larsen, AK

Helboe, L

Christensen, S

Pedersen, LO

Nielsen, M

Torup, L

Sager, T

Sfacteria, A

Erbayraktar, S

Erbayraktar, Z

Gokmen, N

Yilmaz, O

Cerami-Hand, C

Xie, QW

Coleman, T

Cerami, A ^{[1
]}

Brines, M

机构：

[1] Kenneth S Warren Inst, Ossining, NY 10562 USA

[2] H Lundbeck & Co AS, DK-2500 Copenhagen, Denmark

[3] Mario Negri Inst Pharmacol Res, I-20157 Milan, Italy

[4] Univ Messina, I-98122 Messina, Italy

[5] CNR, Inst Neurosci, I-20129 Milan, Italy

[6] Dokuz Eylul Univ, Sch Med, TR-35340 Izmir, Turkey

[7] Warren Pharmaceut Inc, Ossining, NY 10562 USA

来源：

SCIENCE | 2004年 / 305卷 / 5681期

关键词：

D O I：

10.1126/science.1098313

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 [理学]; 0710 [生物学]; 09 [农学];

摘要：

Erythropoietin (EPO) is both hematopoietic and tissue protective, putatively through interaction with different receptors. We generated receptor subtype selective ligands allowing the separation of EPO's bioactivities at the cellular level and in animals. Carbamylated EPO (CEPO) or certain EPO mutants did not bind to the classical EPO receptor ( EPOR) and did not show any hematopoietic activity in human cell signaling assays or upon chronic dosing in different animal species. Nevertheless, CEPO and various nonhematopoietic mutants were cytoprotective in vitro and conferred neuroprotection against stroke, spinal cord compression, diabetic neuropathy, and experimental autoimmune encephalomyelitis at a potency and efficacy comparable to EPO.

引用

页码：239 / 242

页数：4

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