Proteomic-Based Analysis of Hypoxia- and Physioxia-Responsive Proteins and Pathways in Diffuse Large B-Cell Lymphoma.
Proteomic-Based Analysis of Hypoxia- and Physioxia-Responsive Proteins and Pathways in Diffuse Large B-Cell Lymphoma.
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DOI：
10.3390/cells10082025
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发表时间：
2021-08-08
期刊：
影响因子：
6
通讯作者：
Wiśniewski JR
中科院分区：
文献类型：
--
作者：
Duś-Szachniewicz K;Gdesz-Birula K;Zduniak K;Wiśniewski JR
缺氧是大多数肿瘤的共同特征，包括血液恶性肿瘤。目前缺乏对缺氧和物理氧诱导的淋巴瘤整体蛋白质组变化的研究。在这里，我们试图探讨弥漫性大B细胞淋巴瘤（DLBCL）的蛋白质组如何变化时，细胞暴露于急性缺氧应激（1%的O2）和物理氧（5%的O2）长时间。通过LC-MS/MS共鉴定了8239种蛋白质，其中718、513和486种蛋白质在Ri-1、U2904和U2932细胞系中分别具有显著的丰度变化。我们观察到，在B-NHL蛋白质组的变化引起的缺氧和physioxia在每个细胞系的定量相似，但是，差异丰富的蛋白质（DAP）是特定于某一细胞系。一个显着下调的几个核糖体蛋白表明新的核糖体蛋白合成在缺氧的翻译抑制，这是在途径富集分析证实。此外，下调的蛋白质突出了细胞周期，代谢和干扰素信号的改变。正如预期的那样，上调蛋白的富集揭示了与代谢、HIF 1信号传导和氧化应激反应相关的术语。根据我们的研究结果，生理氧诱导较弱的蛋白质丰度的变化相比，由缺氧引起的。我们的数据为了解DLBCL细胞对可变氧水平的反应机制提供了新的证据。此外，这项研究揭示了多种缺氧反应蛋白在缺氧和生理氧化DLBCL中显示出改变的丰度。在常氧和生理氧条件下DLBCL蛋白质组的变化是否对淋巴瘤的发生和进展有功能性影响仍有待研究。
Hypoxia is a common feature in most tumors, including hematological malignancies. There is a lack of studies on hypoxia- and physioxia-induced global proteome changes in lymphoma. Here, we sought to explore how the proteome of diffuse large B-cell lymphoma (DLBCL) changes when cells are exposed to acute hypoxic stress (1% of O2) and physioxia (5% of O2) for a long-time. A total of 8239 proteins were identified by LC–MS/MS, of which 718, 513, and 486 had significant changes, in abundance, in the Ri-1, U2904, and U2932 cell lines, respectively. We observed that changes in B-NHL proteome profiles induced by hypoxia and physioxia were quantitatively similar in each cell line; however, differentially abundant proteins (DAPs) were specific to a certain cell line. A significant downregulation of several ribosome proteins indicated a translational inhibition of new ribosome protein synthesis in hypoxia, what was confirmed in a pathway enrichment analysis. In addition, downregulated proteins highlighted the altered cell cycle, metabolism, and interferon signaling. As expected, the enrichment of upregulated proteins revealed terms related to metabolism, HIF1 signaling, and response to oxidative stress. In accordance to our results, physioxia induced weaker changes in the protein abundance when compared to those induced by hypoxia. Our data provide new evidence for understanding mechanisms by which DLBCL cells respond to a variable oxygen level. Furthermore, this study reveals multiple hypoxia-responsive proteins showing an altered abundance in hypoxic and physioxic DLBCL. It remains to be investigated whether changes in the proteomes of DLBCL under normoxia and physioxia have functional consequences on lymphoma development and progression.
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影响因子：
7.5
作者：
Antebi B;Rodriguez LA 2nd;Walker KP 3rd;Asher AM;Kamucheka RM;Alvarado L;Mohammadipoor A;Cancio LC
通讯作者：
Cancio LC
影响因子：
5.7
作者：
Dennis JE;Whitney GA;Rai J;Fernandes RJ;Kean TJ
通讯作者：
Kean TJ
影响因子：
30.8
作者：
Bhandari, Vinayak;Hoey, Christianne;Bristow, Robert G.
通讯作者：
Bristow, Robert G.
影响因子：
2.6
作者：
Clapper, Erin;Di Trapani, Giovanna;Tonissen, Kathryn F.
通讯作者：
Tonissen, Kathryn F.
影响因子：
3.3
作者：
Adams, Hugo J. A.;de Klerk, John M. H.;Kwee, Thomas C.
通讯作者：
Kwee, Thomas C.