1Department of Neurobiology and Anatomy.
Int J Neurosci. 2013 Oct;123(10):705-10. doi: 10.3109/00207454.2013.795149. Epub 2013 Jun 17.
Glial-cell-line-derived neurotrophic factor (GDNF) has been shown to protect dopaminergic (DA) neurons against 6-hydroxydopamine (6-OHDA) toxicity. The mechanism underlying the antiapoptosis role of GDNF still needs further studies. We previously observed that nuclear factor-kappaB (NF-κB) signaling pathway, i.e. p65/p52, mediated the antiapoptosis role of GDNF in MN9D cells. Here, the DA cell line MN9D was used to explore the mechanisms underlying NF-κB p65/p52-mediated protection role of GDNF in DA neurons. The results showed that GDNF pretreatment blocked the apoptotic effects induced by 6-OHDA, with the upregulation of the antiapoptotic protein, Bcl-2 and Bcl-w, as well as the downregulation of the proapoptotic proteins, Bax and Bad. Furthermore, when sip100 plasmids were transfected into MN9D cells to inhibit the expression of p100, which was the precursor of p52, the effects of GDNF on upregulating Bcl-2 and Bcl-w were attenuated. These results indicated that GDNF could protect MN9D cells from apoptosis induced by 6-OHDA via upregulating Bcl-2 and Bcl-w expressions and downregulating Bax and Bad expressions. Moreover, NF-κB p65/p52 signaling mediated the effects of GDNF on Bcl-2 and Bcl-w expressions.
胶质细胞源性神经营养因子（GDNF）已被证明可保护多巴胺能（DA）神经元免受 6-羟多巴胺（6-OHDA）毒性的侵害。GDNF 发挥抗细胞凋亡作用的机制仍需要进一步研究。我们之前观察到，核因子-κB（NF-κB）信号通路，即 p65/p52，介导 GDNF 在 MN9D 细胞中的抗细胞凋亡作用。在这里，使用多巴胺神经元细胞系 MN9D 来探讨 NF-κB p65/p52 介导 GDNF 对 DA 神经元保护作用的机制。结果表明，GDNF 预处理可阻断 6-OHDA 诱导的细胞凋亡作用，上调抗凋亡蛋白 Bcl-2 和 Bcl-w，并下调促凋亡蛋白 Bax 和 Bad。此外，当将 sip100 质粒转染到 MN9D 细胞中以抑制 p52 的前体 p100 的表达时，GDNF 上调 Bcl-2 和 Bcl-w 的作用减弱。这些结果表明，GDNF 可通过上调 Bcl-2 和 Bcl-w 的表达以及下调 Bax 和 Bad 的表达来保护 MN9D 细胞免受 6-OHDA 诱导的凋亡。此外，NF-κB p65/p52 信号通路介导了 GDNF 对 Bcl-2 和 Bcl-w 表达的影响。
