Modulation of FoxO1 phosphorylation/acetylation by baicalin during aging
Modulation of FoxO1 phosphorylation/acetylation by baicalin during aging
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DOI：
10.1016/j.jnutbio.2011.07.008
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发表时间：
2012-10-01
影响因子：
5.6
通讯作者：
Chung, Hae Young
中科院分区：
文献类型：
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作者：
Kim, Dae Hyun;Kim, Ji Min;Chung, Hae Young
黄芩苷是一种黄酮类化合物，已知可改变各种氧化还原相关的生物活性。包括其抑制活性物质（RS）产生活性和通过细胞氧化还原调节调节核因子-κ B的能力，所述细胞氧化还原调节具有增强的巯基能力。Fox调节已知参与与细胞死亡和氧化应激反应相关的细胞代谢的各种基因。一个这样的情况是通过激活胰岛素诱导的磷脂酰肌醇3-激酶（PI 3 K/Akt）来阻止FoxO 1的表达，从而导致氧化应激和衰老过程的增加。我们用HEK 293 T培养细胞和24月龄大鼠肾组织分离，用黄芩苷10或20 mg/kg/d处理10天，我们发现黄芩苷增强细胞系统和离体肾组织中的过氧化氢酶，抑制RS的产生。结果还显示，胰岛素信号转导（PI 3 K/Akt），FoxO 1磷酸化/乙酰化和过氧化氢酶和锰超氧化物歧化酶的下调，这两个都是FoxO 1靶向基因的激活。此外。黄芩苷处理的大鼠显示通过PI 3 K/Akt级联和cAMP反应元件结合蛋白结合蛋白（CBP）的FoxO 1乙酰化的FoxO 1磷酸化减少。这些结果有力地表明，黄芩苷治疗影响FoxO 1的磷酸化/乙酰化通过上调PI 3 K/Akt信号转导通过胰岛素在老年大鼠。我们的研究结果进一步表明，黄芩苷调节FoxO 1磷酸化通过PI 3 K/Akt的胰岛素和FoxO 1乙酰化的CBP和SIRT 1的相互作用，导致过氧化氢酶基因表达的变化在衰老过程中。(C)2012 Elsevier Inc. All rights reserved.
Baicalin is a flavonoid known to modify various redox-related biological activities. Included is its ability to suppress reactive species (RS) producing activity and modulate nuclear factor-kappa B through cellular redox regulation with enhanced thiol ability.Fox regulates various genes that are known to be involved in cellular metabolism related to cell death and the oxidative stress response. One such case is the prevention of FoxO1 expression by activated insulin-induced phosphatidylinositol 3-kinase (PI3K/Akt, which leads to increased oxidative stress and aging processes.In the present study, we attempted to elucidate the molecular modulation of antioxidant baicalin on the insulin-induced FoxO1 inactivation. We used HEK293T cultured cells and kidney tissue isolated from 24-month-old rats treated with baicalin at a dose of 10 or 20 mg/kg/day for 10 days.We found that baicalin enhanced catalase and suppressed RS production in cell system and in isolated kidney tissue in contrast to the nontreated aged rats. Results also showed activation of insulin signaling (PI3K/Akt), FoxO1 phosphorylation/acetylation and the down-regulation of catalase and manganese superoxide dismutase, both of which are FoxO1-targeting genes. Furthermore. baicalin-treated rats showed a decreased FoxO1 phosphorylation via PI3K/Akt cascade and FoxO1 acetylation by the cAMP-response element-binding protein binding protein (CBP). These results strongly suggest that treatment with baicalin influenced phosphorylation/acetylation of FoxO1 by up-regulating PI3K/Akt signaling through insulin in aged rats. Our results further reveal that baicalin regulated FoxO1 phosphorylation via PI3K/Akt by insulin and FoxO1 acetylation by the interaction of CBP and SIRT1, leading to changes in catalase gene expression during aging. (C) 2012 Elsevier Inc. All rights reserved.