Recombinant Humanized IgG1 Antibody Protects against oxLDL-Induced Oxidative Stress and Apoptosis in Human Monocyte/Macrophage THP-1 Cells by Upregulation of MSRA via Sirt1-FOXO1 Axis.
Recombinant Humanized IgG1 Antibody Protects against oxLDL-Induced Oxidative Stress and Apoptosis in Human Monocyte/Macrophage THP-1 Cells by Upregulation of MSRA via Sirt1-FOXO1 Axis.
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DOI：
10.3390/ijms231911718
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发表时间：
2022-10-03
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
作者：
氧化低密度脂蛋白（oxLDL）诱导的氧化应激和细胞凋亡被认为是心血管疾病的关键因素。蛋氨酸亚砜还原酶 A (MSRA) 是一种有效的细胞内氧化还原酶，是保护细胞免受氧化损伤的重要因素。在这里，我们首先提供证据表明重组人源化 IgG1 抗体治疗上调 THP-1 细胞中 MSRA 的表达，以防御 oxLDL 诱导的氧化应激和细胞凋亡。还观察到 MSRA 的上调受到叉头盒 O 转录因子 (FOXO1) 的调节，FOXO1 的乙酰化在暴露于 oxLDL 时增加，但在用重组人源化 IgG1 抗体处理时下降。此外，我们还发现沉默信息调节因子 1 (SIRT1) 会抑制 FOXO1 乙酰化。重要的是，SIRT1 或 FOXO1 缺陷会损害重组人源化 IgG1 抗体的抗氧化应激和抗凋亡作用。总之，我们的结果表明重组人源化 IgG1 抗体通过 Sirt1-FOXO1 轴上调 MSRA 发挥其抗氧化应激和抗凋亡功能。
Oxidized low-density lipoprotein (oxLDL)-induced oxidative stress and apoptosis are considered as critical contributors to cardiovascular diseases. Methionine sulfoxide reductase A (MSRA) is a potent intracellular oxidoreductase and serves as an essential factor that protects cells against oxidative damage. Here, we firstly provide evidence that recombinant humanized IgG1 antibody treatment upregulated the expression of MSRA in THP-1 cells to defend against oxLDL-induced oxidative stress and apoptosis. It was also observed that the upregulation of MSRA is regulated by the forkhead box O transcription factor (FOXO1), and the acetylation of FOXO1 increased when exposed to oxLDL but declined when treated with recombinant humanized IgG1 antibody. In addition, we identified that silent information regulator 1 (SIRT1) suppresses FOXO1 acetylation. Importantly, SIRT1 or FOXO1 deficiency impaired the anti-oxidative stress and anti-apoptotic effect of recombinant humanized IgG1 antibody. Together, our results suggest that recombinant humanized IgG1 antibody exerts its anti-oxidative stress and anti-apoptotic function by upregulation of MSRA via the Sirt1-FOXO1 axis.
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DOI：
10.1016/j.ijcha.2018.09.006
发表时间：
2018-12
期刊：
International journal of cardiology. Heart & vasculature
影响因子：
--
作者：
Jackson AO;Regine MA;Subrata C;Long S
通讯作者：
Long S
影响因子：
5.3
作者：
Su J;Zhou H;Liu X;Nilsson J;Fredrikson GN;Zhao M
通讯作者：
Zhao M
影响因子：
5.4
作者：
van Dijk RA;Rijs K;Wezel A;Hamming JF;Kolodgie FD;Virmani R;Schaapherder AF;Lindeman JH
通讯作者：
Lindeman JH
DOI：
10.1073/pnas.231472998
发表时间：
2001-11-06
影响因子：
11.1
作者：
Moskovitz, J;Bar-Noy, S;Stadtman, ER
通讯作者：
Stadtman, ER
DOI：
10.1073/pnas.032671199
发表时间：
2002-03-05
影响因子：
11.1
作者：
Ruan, H;Tang, XD;Hoshi, T
通讯作者：
Hoshi, T