Montazeri Fatemeh, Esmaeili Abolghasem, Miroliaei Mehran, Moshtaghian Sayed Jamal
Cell and Molecular Biology Division, Department of Biology, Faculty of Sciences, University of Isfahan, Isfahan, Iran.
J Spinal Cord Med. 2013 May;36(3):231-6. doi: 10.1179/2045772312Y.0000000077.
Induction of p75 neurotrophin receptor (p75NTR) could be one of the first steps that initiate apoptotic cascade after injury, or it may indicate regeneration responses undertaken by the injured system, possibly in collaboration with resident tropomyosin-receptor-kinase (Trk).
To measure quantitative changes in messenger RNA (mRNA) expression levels of p75NTR, Trk A, and caspase-9 in rat's injured spinal cord (SCI). The reciprocal interaction between Trk and p75NTR signaling pathways can dictate cellular responses to neurotrophins. p75NTR can regulate Trk-dependent responses, but the role of Trk in regulating p75NTR-dependent signaling is not well documented.
Using real-time polymerase chain reaction, this study analyzed changes in the mRNA abundance of the mentioned genes at 6, 24, and 72 hours and 7 and 10 days after SCI in adult male rats. SCI was induced at T9 level by transsection.
Results show a complicated temporal and spatial pattern of alteration with different degrees and direction (up- or down-regulation) in p75NTR, Trk A, and caspase-9 mRNA expression levels after SCI. The greatest variation was seen in center regions following SCI. This study shows that alteration in p75NTR, Trk A, and caspase-9 expression starts as early as 6 hours after SCI. Alterations in p75NTR, Trk A, and caspase-9 expression within the spinal cord may play a key role in the apoptotic cell death.
Results suggest that the role of p75NTR is to eliminate damaged cells by activating the apoptotic machinery, especially at the center of damage and during first week after injury.
p75神经营养因子受体(p75NTR)的诱导可能是损伤后启动凋亡级联反应的第一步,或者它可能表明受损系统所采取的再生反应,可能与驻留的原肌球蛋白受体激酶(Trk)协同作用。
测量大鼠脊髓损伤(SCI)后p75NTR、Trk A和半胱天冬酶-9信使核糖核酸(mRNA)表达水平的定量变化。Trk和p75NTR信号通路之间的相互作用可以决定细胞对神经营养因子的反应。p75NTR可以调节Trk依赖的反应,但Trk在调节p75NTR依赖信号传导中的作用尚未得到充分记录。
本研究采用实时聚合酶链反应,分析成年雄性大鼠SCI后6、24和72小时以及7和10天上述基因mRNA丰度的变化。通过横断在T9水平诱导SCI。
结果显示,SCI后p75NTR、Trk A和半胱天冬酶-9 mRNA表达水平呈现出复杂的时空变化模式,具有不同程度和方向(上调或下调)。SCI后中心区域变化最大。本研究表明,p75NTR、Trk A和半胱天冬酶-9的表达变化在SCI后6小时就开始了。脊髓内p75NTR、Trk A和半胱天冬酶-9的表达变化可能在凋亡性细胞死亡中起关键作用。
结果表明,p75NTR的作用是通过激活凋亡机制来清除受损细胞,尤其是在损伤中心和损伤后的第一周。