Manecka Destiny-Love, Lelièvre Vincent, Anouar Youssef
Inserm, U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Mont-Saint-Aignan, France; Institute for Research and Innovation in Biomedicine, Normandy University, University of Rouen, Mont-Saint-Aignan, France.
CNRS, UPR 3212, INCI, Strasbourg, France.
FEBS Lett. 2014 Aug 25;588(17):3008-14. doi: 10.1016/j.febslet.2014.06.009. Epub 2014 Jun 10.
The pituitary adenylate cyclase-activating polypeptide (PACAP) is a trophic neuropeptide that promotes cell survival and neuritogenesis in the central and peripheral nervous system. Our previous transcriptomic studies revealed the down-regulation of the cytokine tumor necrosis factor (TNF) during PACAP-induced PC12 cell differentiation. Here we show that TNF is constitutively expressed in PC12 cells in a manner dependent on NF-κB transcription factor, and that PACAP rapidly inhibits TNF expression and secretion. The inhibition occurs through suppression of RelB subunit of NF-κB, and is likely to prevent the deleterious effects of the cytokine on survival and neurite outgrowth during PC12 cell differentiation.
垂体腺苷酸环化酶激活多肽（PACAP）是一种营养神经肽，可促进中枢和外周神经系统中的细胞存活和神经突生成。我们之前的转录组学研究表明，在PACAP诱导的PC12细胞分化过程中，细胞因子肿瘤坏死因子（TNF）表达下调。在此我们表明，TNF在PC12细胞中以依赖于NF-κB转录因子的方式组成性表达，并且PACAP可迅速抑制TNF的表达和分泌。这种抑制通过抑制NF-κB的RelB亚基发生，并且可能在PC12细胞分化过程中防止细胞因子对存活和神经突生长的有害影响。
