核桃多酚和活性代谢物尿石素 A 通过上调 PKA/CREB/BDNF 信号改善 SH-SY5Y 细胞的氧化损伤,Food & Function

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核桃多酚和活性代谢物尿石素 A 通过上调 PKA/CREB/BDNF 信号改善 SH-SY5Y 细胞的氧化损伤
Food & Function ( IF 5.1 ) Pub Date : 2022-12-27 , DOI: 10.1039/d2fo03310k
Lei An ₁ , Mengxue Li _{1,

2,

3} , Cunen Zou _{1,

2,

3} , Ke Wang _{1,

2,

3} , Wei Zhang ₁ , Xiaolong Huang ₁ , Yousheng Wang _{1,

2,

3}

Affiliation

越来越多的证据证实了核桃饮食对随着年龄增长维持大脑功能的健康益处。最近的研究表明，核桃多酚 (WP) 及其活性代谢物尿石素可能在核桃饮食的健康益处中发挥重要作用。在本研究中，我们评估了 WP 和尿石素 A (UroA) 对 H ₂ O ₂诱导的人神经母细胞瘤 (SH-SY5Y) 细胞损伤的保护作用，并研究了其在 cAMP 反应元件结合蛋白 (CREB) 中的机制) 介导的信号通路，它与神经退行性疾病和神经系统疾病密切相关。结果表明，WP（50 和 100 μg·mL ^-1) 和 UroA（5 和 10 μM）处理可显着逆转细胞活力下降、细胞外乳酸脱氢酶 (LDH) 渗漏、细胞内钙超载和 H 2 O 2 处理诱导_的细胞_凋亡。此外，WP 和 UroA 治疗还减轻了 H ₂ O ₂诱导的氧化应激，包括细胞内活性氧 (ROS) 的过量产生以及超氧化物歧化酶 (SOD) 和过氧化氢酶 (CAT) 的活性降低。此外，蛋白质印迹分析表明，WP 和 UroA 处理显着增加了 cAMP 依赖性蛋白激酶 A (PKA) 的活性和 pCREB (Ser133) 及其下游分子脑源性神经营养因子 (BDNF) 的表达，这些都随着H₂ O₂处理。此外，用 PKA 抑制剂 H89 预处理消除了 WP 和 UroA 的保护作用，表明 PKA/CREB/BDNF 神经营养信号通路的上调是它们对氧化应激的神经保护作用所必需的。目前的工作为理解 WP 和 UroA 对脑功能的有益作用提供了新的视角，值得进一步研究。

"点击查看英文标题和摘要"

Walnut polyphenols and the active metabolite urolithin A improve oxidative damage in SH-SY5Y cells by up-regulating PKA/CREB/BDNF signaling

Accumulating evidence has confirmed the health benefits of walnut diets in maintaining brain function with age. Recent studies have indicated that walnut polyphenols (WP) and their active metabolites urolithins may play an important role in the health benefits of walnut diets. In the present study, we evaluated the protective effect of WP and urolithin A (UroA) on H₂O₂-induced damage in human neuroblastoma (SH-SY5Y) cells, and investigated its mechanisms in the cAMP-response element binding protein (CREB)-mediated signaling pathway, which is tightly involved in neurodegenerative and neurological diseases. The results demonstrated that both WP (50 and 100 μg mL⁻¹) and UroA (5 and 10 μM) treatment significantly reversed the decrease of cell viability, the leakage of extracellular lactate dehydrogenase (LDH), the overload of intracellular calcium and cell apoptosis induced by H₂O₂ treatment. Moreover, WP and UroA treatment also relieved H₂O₂-induced oxidative stress including overproduction of intracellular reactive oxygen species (ROS) and reduced activities of superoxide dismutase (SOD) and catalase (CAT). Additionally, western blot analysis showed that WP and UroA treatment significantly increased the activity of cAMP-dependent protein kinase A (PKA) and the expression of pCREB (Ser133) and its downstream molecule brain-derived neurotrophic factor (BDNF), which were decreased by H₂O₂ treatment. Furthermore, pretreatment with the PKA inhibitor H89 abolished the protective effects of WP and UroA, indicating that up-regulation of the PKA/CREB/BDNF neurotrophic signaling pathway is required for their neuroprotective effects against oxidative stress. The current work provides new perspectives for understanding the beneficial effects of WP and UroA on brain function, which warrants further investigation.

更新日期：2022-12-27

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