Chaverneff Florence, Barrett John
Neuroscience Program, University of Miami Miller School of Medicine, Miami, Florida 33136, USA.
J Neurochem. 2009 May;109(3):733-43. doi: 10.1111/j.1471-4159.2009.05990.x. Epub 2009 Feb 13.
The combination of bone morphogenetic protein 7 (BMP7) and neurotrophins (e.g. brain-derived neurotrophic factor, BDNF) protects septal neurons during hypoglycemic stress. We investigated the signaling mechanisms underlying this synergistic protection. BMP7 (5 nM) increased phosphorylation and nuclear translocation of BMP-responsive Smads 1/5/8 within 30 min in cultures of rat embryonic septal neurons. BDNF (100 ng/mL) enhanced the BMP7-induced increase in phospho-Smad levels in both nucleus and cytoplasm; this effect was more pronounced after a hypoglycemic stress. BDNF increased both Akt and Erk phosphorylation, but pharmacological blockade of these kinase pathways (with wortmannin and U0126, respectively) did not reduce the Smad phosphorylation produced by the BMP7 + BDNF combination. Inhibitors of casein kinase II (CK2) activity reduced the (BMP7 + BDNF)-induced Smad phosphorylation, and this trophic factor combination increased CK2 activity in hypoglycemic cultures. These findings suggest that BDNF can increase BMP-dependent Smad phosphorylation via a mechanism requiring CK2.
骨形态发生蛋白7（BMP7）与神经营养因子（如脑源性神经营养因子，BDNF）联合使用可在低血糖应激期间保护中隔神经元。我们研究了这种协同保护作用背后的信号传导机制。在大鼠胚胎中隔神经元培养物中，BMP7（5 nM）在30分钟内增加了BMP反应性Smads 1/5/8的磷酸化和核转位。BDNF（100 ng/mL）增强了BMP7诱导的细胞核和细胞质中磷酸化Smad水平的增加；在低血糖应激后这种作用更为明显。BDNF增加了Akt和Erk的磷酸化，但分别用渥曼青霉素和U0126对这些激酶途径进行药理学阻断并没有降低BMP7 + BDNF组合产生的Smad磷酸化。酪蛋白激酶II（CK2）活性抑制剂降低了（BMP7 + BDNF）诱导的Smad磷酸化，并且这种营养因子组合增加了低血糖培养物中的CK2活性。这些发现表明，BDNF可通过一种需要CK2的机制增加BMP依赖性Smad磷酸化。
