Gunawardana Piyumi B Wijesiri, Gohil Khyati, Moon Kyung-Mee, Foster Leonard J, Williams Florence J
Department of Chemistry, University of Iowa, Iowa City, IA, USA.
Department of Chemistry, University of Alberta, Edmonton, AB, Canada.
Mol Neurobiol. 2025 Mar 14. doi: 10.1007/s12035-025-04772-1.
In an effort to gain insight into cellular systems impacted by neurotrophic trans-banglene (t-BG), global proteomic profiling and Western blot analyses were employed. Expression level changes in response to t-BG treatment were compared to those observed with nerve growth factor (NGF), a natural neurotrophic protein and functional analog to t-BG. Findings from these studies did not point to direct interception of NGF/TrkA signaling by t-BG. Instead, significant alterations in iron-binding and iron-regulating proteins were observed. While total iron levels showed no change across all treatments, intracellular iron measurements and mitochondrial iron measurements demonstrated lower ferrous (Fe) ion levels in t-BG treated cells but not in NGF treated cells. These results highlight a potential connection between iron regulation and neurotrophic activity, a relationship which has, to date, not been well studied. These results are also notable given that iron dysregulation occurs in most neurodegenerative disease settings, and that iron has been shown to facilitate protein aggregation and apoptotic mechanisms.
为了深入了解受神经营养性反式孟加拉烯（t-BG）影响的细胞系统，我们采用了全局蛋白质组分析和蛋白质印迹分析。将t-BG处理后的表达水平变化与神经生长因子（NGF）（一种天然神经营养蛋白，是t-BG的功能类似物）处理后的观察结果进行了比较。这些研究结果并未表明t-BG直接拦截NGF/TrkA信号传导。相反，观察到铁结合蛋白和铁调节蛋白发生了显著变化。虽然所有处理组的总铁水平均无变化，但细胞内铁测量和线粒体铁测量显示，t-BG处理的细胞中亚铁（Fe）离子水平较低，而NGF处理的细胞中则没有。这些结果突出了铁调节与神经营养活性之间的潜在联系，迄今为止，这种关系尚未得到充分研究。鉴于大多数神经退行性疾病都存在铁调节异常，并且铁已被证明会促进蛋白质聚集和凋亡机制，这些结果也值得关注。
