Lab. Microbiome Immunobiology, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, R. Weigla 12, 53-114, Wrocław, Poland.
Bioengineering Research Group, Łukasiewicz Research Network-PORT Polish Center for Technology Development, 54-066, Wroclaw, Poland.
Mol Neurobiol. 2023 May;60(5):2819-2831. doi: 10.1007/s12035-023-03246-6. Epub 2023 Feb 3.
Food-derived bioactive peptides able to regulate neuronal function have been intensively searched and studied for their potential therapeutic application. Our previous study showed that a polypeptide complex yolkin, isolated from hen egg yolk as a fraction accompanying immunoglobulin Y (IgY), improved memory and cognitive functions in rats. However, the mechanism activated by the yolkin is not explained. The goal of the present study was to examine what molecular mechanism regulating brain-derived neurotrophic factor (BDNF) expression is activated by the yolkin complex, using in vitro models of PC12 cell line and fetal rat hippocampal cell line H19-7. It was shown that yolkin increased the proliferative activity of rat hippocampal precursor cells H19-7 cells and upregulated the expression/production of BDNF in a cyclic adenosine monophosphate (cAMP)-response element-binding protein (CREB)-dependent manner. Additionally the upregulation of carboxypeptidase E/neurotrophic factor-α1 (CPE/(NF-α1) expression was shown. It was also determined that upregulation of CREB phosphorylation by yolkin is dependent on cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) and phosphoinositide 3-kinases/protein kinase B (PI3K/Akt) signaling pathway activation. Moreover, the impact of yolkin on the level of intracellular Ca, nitric oxide, and activation of extracellular signal-regulated kinases 1/2 (ERK 1/2 kinase) was excluded. These results emphasize that yolkin can act comprehensively and in many directions and may participate in the regulation of neurons' survival and activity. Therefore, it seems that the yolkin specimen can be used in the future as a safe, bioavailable, natural nutraceutical helping to improve the cognition of older people.
从食物中提取的具有调节神经元功能的生物活性肽因其潜在的治疗应用而受到广泛研究。我们之前的研究表明，一种从鸡卵黄中分离出来的多肽复合物 yolkin，作为免疫球蛋白 Y（IgY）的伴随物，能够改善大鼠的记忆和认知功能。然而， yolkin 激活的机制尚未得到解释。本研究的目的是使用 PC12 细胞系和胎鼠海马细胞系 H19-7 的体外模型，研究 yolkin 复合物激活哪种分子机制来调节脑源性神经营养因子（BDNF）的表达。结果表明， yolkin 增加了大鼠海马前体细胞 H19-7 细胞的增殖活性，并通过环磷酸腺苷（cAMP）反应元件结合蛋白（CREB）依赖性方式上调 BDNF 的表达/产生。此外，还显示羧肽酶 E/神经营养因子-α1（CPE/（NF-α1）的表达上调。还确定 yolkin 通过 cAMP/蛋白激酶 A（cAMP/PKA）和磷酸肌醇 3-激酶/蛋白激酶 B（PI3K/Akt）信号通路激活而上调 CREB 磷酸化。此外， yolkin 对细胞内 Ca、一氧化氮水平和细胞外信号调节激酶 1/2（ERK 1/2 激酶）激活的影响被排除在外。这些结果强调 yolkin 可以全面且多方向地发挥作用，可能参与调节神经元的存活和活性。因此， yolkin 样品似乎可以在未来作为一种安全、生物可利用的天然营养保健品，帮助改善老年人的认知能力。
