A role for HSP27 in sensory neuron survival
A role for HSP27 in sensory neuron survival
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DOI：
10.1523/jneurosci.19-20-08945.1999
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发表时间：
1999-10-15
影响因子：
5.3
通讯作者：
Woolf, CJ
中科院分区：
文献类型：
--
作者：
Lewis, SE;Mannion, RJ;Woolf, CJ
新生大鼠的周围神经损伤导致大多数轴突切断的感觉神经元在损伤后7天死亡。然而，在成年动物中，所有感觉神经元在轴突切断后至少存活4个月。感觉神经元如何获得轴突损伤后的存活能力尚不清楚。在这里，我们描述了如何表达的小热休克蛋白27（HSP 27）与神经元存活轴突切断后，在体内和神经生长因子撤出后，在体外。出生时L4背根节内HSP 27免疫反应阳性神经元的数量较低，在出生后0天（P0）坐骨神经切断后21天内没有明显变化。相反，在成人中，所有轴突切断的神经元开始表达HSP 27。P0坐骨神经切片后一周，L4 DRG中的神经元总数显著减少，但所有存活的轴突切断神经元，如通过c-jun免疫反应性所鉴定的，对HSP 27具有免疫反应性。此外，末端脱氧核苷酸转移酶介导的dUTP缺口末端标记显示，非常少的HSP 27表达神经元死亡后48小时新生儿轴突切断。在体外，HSP 27的表达和生存之间存在类似的相关性，在P0 DRG培养，神经元表达HSP 27优先生存神经生长因子撤出。最后，过度表达人HSP 27在新生大鼠感觉和交感神经元显着增加神经生长因子撤退后的生存，有近两倍的神经元存活在48 hr. Together这些结果表明，HSP 27在感觉神经元起着促进生存轴突切断或神经营养因子撤退后的作用。
Peripheral nerve injury in neonatal rats results in the death of the majority of the axotomized sensory neurons by 7 d after injury. In adult animals, however, all sensory neurons survive for at least 4 months after axotomy. How sensory neurons acquire the capacity to survive axonal injury is not known. Here we describe how the expression of the small heat shock protein 27 (HSP27) is correlated with neuronal survival after axotomy in vivo and after NGF withdrawal in vitro. The number of HSP27-immunoreactive neurons in the L4 DRG is low at birth and does not change significantly for 21 d after postnatal day 0 (P0) sciatic nerve axotomy. In contrast, in the adult all axotomized neurons begin to express HSP27. One week after P0 sciatic nerve section the total number of neurons in the L4 DRG is dramatically reduced, but all surviving axotomized neurons, as identified by c-jun immunoreactivity, are immunoreactive for HSP27. In addition, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling reveals that very few HSP27-expressing neurons are dying 48 hr after neonatal axotomy. In vitro, a similar correlation exists between HSP27 expression and survival; in P0 DRG cultures, neurons that express HSP27 preferentially survive NGF withdrawal. Finally, overexpression of human HSP27 in neonatal rat sensory and sympathetic neurons significantly increases survival after NGF withdrawal, with nearly twice as many neurons surviving at 48 hr. Together these results suggest that HSP27 in sensory neurons plays a role in promoting survival after axotomy or neurotrophin withdrawal.