Proteomic-Based Analysis of Hypoxia- and Physioxia-Responsive Proteins and Pathways in Diffuse Large B-Cell Lymphoma
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 a...
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MDPI AG
2021-08-01
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| author | Kamila Duś-Szachniewicz Katarzyna Gdesz-Birula Krzysztof Zduniak Jacek R. Wiśniewski |
| author_facet | Kamila Duś-Szachniewicz Katarzyna Gdesz-Birula Krzysztof Zduniak Jacek R. Wiśniewski |
| author_sort | Kamila Duś-Szachniewicz |
| collection | DOAJ |
| description | 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 O<sub>2</sub>) and physioxia (5% of O<sub>2</sub>) 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. |
| first_indexed | 2024-03-10T08:55:47Z |
| format | Article |
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| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T08:55:47Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
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| series | Cells |
| spelling | doaj.art-af29002ec8424014b176bfd4c96909112023-11-22T07:10:40ZengMDPI AGCells2073-44092021-08-01108202510.3390/cells10082025Proteomic-Based Analysis of Hypoxia- and Physioxia-Responsive Proteins and Pathways in Diffuse Large B-Cell LymphomaKamila Duś-Szachniewicz0Katarzyna Gdesz-Birula1Krzysztof Zduniak2Jacek R. Wiśniewski3Department of Clinical and Experimental Pathology, Institute of General and Experimental Pathology, Wrocław Medical University, Marcinkowskiego 1, 50-368 Wrocław, PolandDepartment of Clinical and Experimental Pathology, Institute of General and Experimental Pathology, Wrocław Medical University, Marcinkowskiego 1, 50-368 Wrocław, PolandDepartment of Clinical and Experimental Pathology, Institute of General and Experimental Pathology, Wrocław Medical University, Marcinkowskiego 1, 50-368 Wrocław, PolandBiochemical Proteomics Group, Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, 82152 Martinsried, GermanyHypoxia 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 O<sub>2</sub>) and physioxia (5% of O<sub>2</sub>) 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.https://www.mdpi.com/2073-4409/10/8/2025hypoxiaphysioxiadiffuse large B-cell lymphoma (DLBCL)B-cell non-Hodgkin lymphomas (B-NHL)label-free quantitative proteomicsprotein–protein interaction network (PPIN) |
| spellingShingle | Kamila Duś-Szachniewicz Katarzyna Gdesz-Birula Krzysztof Zduniak Jacek R. Wiśniewski Proteomic-Based Analysis of Hypoxia- and Physioxia-Responsive Proteins and Pathways in Diffuse Large B-Cell Lymphoma Cells hypoxia physioxia diffuse large B-cell lymphoma (DLBCL) B-cell non-Hodgkin lymphomas (B-NHL) label-free quantitative proteomics protein–protein interaction network (PPIN) |
| title | Proteomic-Based Analysis of Hypoxia- and Physioxia-Responsive Proteins and Pathways in Diffuse Large B-Cell Lymphoma |
| title_full | Proteomic-Based Analysis of Hypoxia- and Physioxia-Responsive Proteins and Pathways in Diffuse Large B-Cell Lymphoma |
| title_fullStr | Proteomic-Based Analysis of Hypoxia- and Physioxia-Responsive Proteins and Pathways in Diffuse Large B-Cell Lymphoma |
| title_full_unstemmed | Proteomic-Based Analysis of Hypoxia- and Physioxia-Responsive Proteins and Pathways in Diffuse Large B-Cell Lymphoma |
| title_short | Proteomic-Based Analysis of Hypoxia- and Physioxia-Responsive Proteins and Pathways in Diffuse Large B-Cell Lymphoma |
| title_sort | proteomic based analysis of hypoxia and physioxia responsive proteins and pathways in diffuse large b cell lymphoma |
| topic | hypoxia physioxia diffuse large B-cell lymphoma (DLBCL) B-cell non-Hodgkin lymphomas (B-NHL) label-free quantitative proteomics protein–protein interaction network (PPIN) |
| url | https://www.mdpi.com/2073-4409/10/8/2025 |
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