Fucoxanthin Alleviates Oxidative Stress through Akt/Sirt1/FoxO3α Signaling to Inhibit HG-Induced Renal Fibrosis in GMCs
Fucoxanthin Alleviates Oxidative Stress through Akt/Sirt1/FoxO3α Signaling to Inhibit HG-Induced Renal Fibrosis in GMCs
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DOI：
10.3390/md17120702
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发表时间：
2019-12
期刊：
影响因子：
5.4
通讯作者：
Guanyu Yang;L. Jin;D. Zheng;Xiaoliang Tang;Junwei Yang;L. Fan;Xi Xie
中科院分区：
文献类型：
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作者：
Guanyu Yang;L. Jin;D. Zheng;Xiaoliang Tang;Junwei Yang;L. Fan;Xi Xie
岩藻黄质是一种主要的海洋类胡萝卜素，具有很强的抗氧化活性。FoxO 3 α是叉头盒O家族转录因子中的一员，通过调节氧化应激在糖尿病肾病中发挥重要作用。FoxO 3 α的活性与其磷酸化和乙酰化状态有关，受Akt和Sirt 1（赖氨酸脱乙酰酶）调节。本研究旨在探讨岩藻黄质是否通过FoxO 3 α减轻DN的氧化应激和纤维化，以及Akt和Sirt 1是否参与其中。我们发现，在HG中培养的GMCs中，岩藻黄质处理显著降低FN和胶原IV的表达，以及活性氧的产生，这表明岩藻黄质有利于减轻DN中的纤维化和氧化应激。此外，我们还发现岩藻黄质降低了FoxO 3 α的磷酸化和乙酰化水平，逆转了HG对FoxO 3 α蛋白水平的抑制，进而促进了FoxO 3 α的核转运。此外，岩藻黄素还能促进FoxO 3 α下游靶基因锰超氧化物歧化酶的表达。此外，我们发现岩藻黄质逆转Akt的激活和Sirt 1的抑制。然而，岩藻黄素对FoxO 3 α表达和核转运的增强作用被Akt激活剂SC 79或Sirt 1抑制剂EX 527预处理显著降低。综上所述，我们的研究探讨了岩藻黄质通过Akt/Sirt 1/FoxO 3 α信号通路减轻HG诱导的氧化应激和纤维化，提示岩藻黄质是一种潜在的DN治疗策略。
As one of the main marine carotenoids, fucoxanthin has strong antioxidant activity. FoxO3α, a member of the forkhead box O family of transcription factors, plays an important role in DN by regulating oxidative stress. The activity of FoxO3α is related to its phosphorylation and acetylation status, regulated by Akt and Sirt1, a lysine deacetylase. Our study aimed to investigate whether fucoxanthin could alleviate oxidative stress and fibrosis via FoxO3α in DN and whether Akt and Sirt1 were involved. We found that in GMCs cultured in HG, fucoxanthin treatment significantly reduced the expression of FN and collagen IV, as well as reactive oxygen species generation, suggesting that fucoxanthin is beneficial to alleviate both fibrosis and oxidative stress in DN. In addition, we found that fucoxanthin decreased the phosphorylation and acetylation level of FoxO3α, reversed the protein level of FoxO3α inhibited by HG, and then promoted the nuclear transport of FoxO3α. Besides, fucoxanthin promoted the expression of manganese superoxide dismutase, a downstream target of FoxO3α. Furthermore, we found that fucoxanthin reversed the activation of Akt and inhibition of Sirt1. However, the enhancement of fucoxanthin in FoxO3α expression and nuclear transport was significantly decreased by pretreatment with Akt activator SC79 or Sirt1 inhibitor EX527. In summary, our study explored fucoxanthin alleviated oxidative stress and fibrosis induced by HG through Akt/Sirt1/FoxO3α signaling in GMCs, suggesting fucoxanthin is a potential therapeutic strategy for DN.