IMMUNOSUPPRESSANT FK506 PROMOTES NEURITE OUTGROWTH IN CULTURES OF PC12 CELLS AND SENSORY GANGLIA

被引：279
作者：
LYONS, WE
GEORGE, EB
DAWSON, TM
STEINER, JP
SNYDER, SH
机构：
[1] JOHNS HOPKINS UNIV,SCH MED,DIV TOXICOL SCI,BALTIMORE,MD 21205
[2] JOHNS HOPKINS UNIV,SCH MED,DEPT PHARMACOL & MOLEC SCI,BALTIMORE,MD 21205
[3] JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21205
[4] JOHNS HOPKINS UNIV,SCH MED,DEPT PSYCHIAT & BEHAV SCI,BALTIMORE,MD 21205
[5] JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21205
来源：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 1994年 / 91卷 / 08期
关键词：
CYCLOPHILIN; IMMUNOPHILIN; NERVE GROWTH FACTOR; NEURODEGENERATION; NEURAL REGENERATION;
D O I：
10.1073/pnas.91.8.3191
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：
The immunosuppressant drug FK506 acts by binding to receptor proteins, FK506-binding proteins (FKBPs), which in turn can bind to and regulate a Ca2+-dependent phosphatase, calcineurin, and a Ca2+ release channel, the ryanodine receptor. Based on our findings in regeneration models that levels of FKBPs during neural regeneration parallel those of growth-associated protein GAP43, a calcineurin substrate that regulates neurite extension, we examined effects of FK506 in PC12 rat pheochromocytoma cells and in rat sensory ganglia. FK506 enhances neurite outgrowth in both systems by increasing sensitivity to nerve growth factor. Blockade of FK506 actions in sensory ganglia by rapamycin, an FK506 antagonist, establishes that these effects involve FKBPs. Rapamycin itself stimulates neurite outgrowth in PC12 cells. These drug effects are detected at subnanomolar concentrations, suggesting therapeutic application in diseases involving neural degeneration.
引用
收藏
页码：3191 / 3195
页数：5
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