Table 1.
Summary of all relevant studies related to proteomics of CaOx crystal–cell interactions.
| Year | Authors/Reference | Conditions of Crystal–Cell Interactions | Proteomics Technologies/Functional Assays | Main Findings |
|---|---|---|---|---|
| Effects of differential doses and types of CaOx crystals on cellular proteome of renal tubular cells | ||||
| 2008 | Semangoen T, et al. [24] | Cell: MDCK cells (whole cells) Crystal: 100 µg/mL COM Incubation: 48 h |
2-DE, Sypro Ruby staining, Q-TOF MS and MS/MS | 11 upregulated and 5 downregulated proteins that play roles in transcription/translation, signal transduction, cellular metabolism and growth, nuclear and cellular structure, transport, stress response, and biosynthesis. |
| 2008 | Thongboonkerd V, et al. [25] | Cell: MDCK cells (whole cells) Crystal: 1000 µg/mL COM Incubation: 48 h |
2-DE, Sypro Ruby staining, Q-TOF MS and MS/MS | 25 upregulated and 23 downregulated proteins were identified. While chaperones were upregulated, other proteins involved in protein synthesis, cell cycle regulation, cell structure, and cellular signaling were downregulated. |
| 2008 | Semangoen T, et al. [26] | Cell: MDCK cells (whole cells) Crystal: 100 µg/mL COD Incubation: 48 h |
2-DE, Sypro Ruby staining, Q-TOF MS and MS/MS | 5 upregulated and 5 downregulated proteins that control cellular metabolism, structure, integrity, signal transduction, and stress response. |
| 2010 | Chen S, et al. [27] | Cell: HK-2 cells (whole cells) Crystal: 200 µg/mL COM Incubation: 12 h |
2-DE, silver diamine staining, LC-ESI MS/MS | 9 upregulated and 3 downregulated proteins with roles in energy production, cell proliferation, apoptosis, stress response, calcium balance, and protein synthesis. |
| 2011 | Chiangjong W, et al. [28] | Cell: MDCK cells (whole cells) Crystal: 100 µg/mL COD Incubation: 48 h |
2-DE, Pro-Q Emerald glycoprotein staining, Sypro Ruby total protein staining, Q-TOF MS and MS/MS | Among 16 significantly altered glycoproteins, glycoforms of three proteasome subunits were upregulated, whereas a glycoform of actin-related protein 3 (ARP3) was downregulated. |
| 2012 | Chaiyarit S, et al. [29] | Cell: MDCK cells (purified mitochondria) Crystal: 100 µg/mL COM Incubation: 48 h |
2-DE, Deep Purple staining, Q-TOF MS and MS/MS, Oxyblot assay | 12 upregulated and 3 downregulated mitochondrial proteins that regulate cell structure, metabolism and energy production. COM crystals also induced mitochondrial dysfunction and accumulation of oxidatively modified proteins in the cells. |
| 2017 | Vinaiphat A, et al. [30] | Cell: MDCK cells (whole cells) Crystal: 100/1000 µg/mL COD/COM Incubation: 48 h |
Protein–protein interactions network analysis, luciferin–luciferase ATP assay, Oxyblot assay, measurement of ubiquitinated proteins, cell death assay, and crystal–cell adhesion assay | High-dose of these crystals caused more obvious changes in cellular proteome than low-dose, and COM was more potent for inducing alterations in cellular proteome than COD. The cells treated with high-dose had greater levels of intracellular ATP, oxidatively modified proteins and cell death, but lower level of ubiquitinated proteins. COM also induced more severe cytotoxicity than COD. Pretreatment of the cells with an antioxidant EGCG could lower the crystal-induced accumulation of oxidatively modified proteins and crystal-binding capability of the cells. |
| 2018 | Peerapen P, et al. [31] | Cell: MDCK cells (whole cells) Crystal: 1000 µg/mL COM Incubation: 48 h |
Protein–protein interactions network analysis, proliferation assay, wound-healing assay, Oxyblot assay, luciferin–luciferase ATP assay, and measurement of trans-epithelial resistance (TER) | The cytotoxic cells treated with 1000 µg/mL COM crystals had decreases in cell proliferation, wound-healing capability, TER, and levels of tight junction protein zonula occludens-1 (ZO-1) and signaling protein RhoA. In contrast, levels of intracellular ATP and oxidatively modified proteins were increased. |
| Proteomic identification of COM crystal receptors on apical surface of renal tubular cells | ||||
| 2011 | Fong-ngern K, et al. [32] | Cell: MDCK cells (purified apical membranes) Crystal: COM Incubation: overnight |
GeLC-MS/MS, Q-TOF MS and MS/MS, crystal–cell adhesion assay, antibody neutralization assay | A total of 96 potential COM crystal receptors were identified. The role for annexin II as the COM crystal receptor was confirmed by neutralization assay using a specific antibody. |
| 2012 | Chutipongtanate S, et al. [33] | Cell: MDCK cells (whole cells and purified apical membranes) Crystal: 100 µg/mL COM Incubation: 30 min, 72 h |
2-DE, Sypro Ruby staining, Q-TOF MS and MS/MS, crystal–cell adhesion assay, calcium induction assay, antibody neutralization assay | Annexin A1 served as the COM crystal receptor. |
| 2013 | Kanlaya R, et al. [34] | Cell: MDCK cells (whole cells and purified apical membranes) Crystal: 100 µg/mL COM Incubation: 30 min, 72 h |
2-DE, Sypro Ruby staining, Q-TOF MS and MS/MS, crystal–cell adhesion assay, oxalate induction assay, antibody neutralization assay | A-enolase served as the COM crystal receptor. |
| 2016 | Peerapen P, et al. [35] | Cell: MDCK cells (whole cells and purified apical membranes) Crystal: 100 µg/mL COM Incubation: 30 min |
Crystal–cell adhesion assay, calcium induction assay | Annexin A1 served as the COM crystal receptor. |
| 2016 | Fong-ngern K, et al. [36] | Cell: MDCK cells (whole cells and purified apical membranes) Crystal: 100 µg/mL COM Incubation: 1 h |
Crystal–cell adhesion assay, antibody neutralization assay | A-enolase served as the COM crystal receptor. |
| 2016 | Fong-ngern K, et al. [37] | Cell: MDCK cells (whole cells and purified apical membranes) Crystal: 100 µg/mL COM Incubation: 1 h, 48 h |
Crystal–cell adhesion assay, crystal internalization assay, antibody neutralization assay, protein knockdown by small interfering RNA (siRNA) | HSP90 served as the COM crystal receptor. |
| 2016 | Manissorn J, et al. [38] | Cell: MDCK cells (whole cells and purified apical membranes) Crystal: 100 µg/mL COM Incubation: 30 min |
Crystal–cell adhesion assay, protein overexpression, oxalate induction assay | A-tubulin overexpression caused downregulation of three COM crystal receptors, including α-enolase, HSP70 and HSP90, and declined crystal-binding capability of the cells. |
| 2016 | Pongsakul N, et al. [39] | Cell: MDCK cells (whole cells) Crystal: 100 µg/mL COM Incubation: 30 min |
Crystal–cell adhesion assay, protein knockdown by siRNA, oxalate induction assay | Lamin A/C knockdown caused reduced levels of four COM crystal receptors, including vimentin, α-enolase, S100 and annexin A2, and declined crystal-binding capability of the cells. |
| 2018 | Manissorn J, et al. [40] | Cell: HEK293T cells (whole cells) Crystal: 100 µg/mL COM Incubation: 1 h |
Crystal–cell adhesion assay, protein knockdown by siRNA | HSP90 served as the COM crystal receptor. |
| 2018 | Vinaiphat A, et al. [41] | Cell: MDCK cells (whole cells and purified apical membranes) Crystal: 100 µg/mL COM Incubation: 1 h |
Crystal–cell adhesion assay, crystal internalization assay, antibody neutralization assay | PMCA2 served as the COM crystal receptor. |
| Effects of COM crystals on cellular proteome of monocytes and macrophages | ||||
| 2010 | Singhto N, et al. [42] | Cell: U937 cells (whole cells) Crystal: 100 µg/mL COM Incubation: 24 h |
2-DE, Deep Purple staining, Q-TOF MS and MS/MS | 9 upregulated proteins and 13 downregulated proteins with roles in cell cycle, cellular structure, carbohydrate metabolism, lipid metabolism, mRNA processing, and protein synthesis, stabilization and degradation. |
| 2013 | Singhto N, et al. [43] | Cell: Human macrophages (whole cells) Crystal: 100 µg/mL COM Incubation: 24 h |
2-DE, Deep Purple staining, Q-TOF MS and MS/MS, phagocytosis assay, protein knockdown by siRNA | 7 upregulated and 7 downregulated proteins that control cellular structure, carbohydrate metabolism, DNA/RNA processing, protein metabolism, molecular trafficking, and stress response. HSP90 played crucial role in phagosome formation and phagocytic activity of macrophages. |
| Effects of COM crystals on secretome and exosomal proteome | ||||
| 2016 | Chiangjong W, et al. [13] | Cell: MDCK cells (secretome) Crystal: 100 µg/mL COM Incubation: 20 h |
2-DE, Deep Purple staining, Q-TOF MS/MS, crystal-migration assay, cell-migration assay | COM crystals induced 2 increased and 4 decreased secretory proteins from renal tubular cells. The increased secretory enolase-1, in turn, enhanced COM crystal invasion through ECM. |
| 2016 | Sintiprungrat K, et al. [44] | Cell: U937 cells (secretome) Crystal: 100 µg/mL COM Incubation: 16 h |
2-DE, Deep Purple staining, Q-TOF MS and MS/MS | COM crystals induced 14 increased and 4 decreased secretory proteins associated with immune response and cell survival from U937 monocytic cells. The increased HSP90 was localized on the cell surface. |
| 2018 | Singhto N, et al. [45] | Cell: Human macrophages (exosomes) Crystal: 100 µg/mL COM Incubation: 24 h |
2-DE, Deep Purple staining, nanoLC-ESI-ETD MS/MS, cell-migration assay, phagocytosis assay, protein knockdown by siRNA | 2 upregulated and 4 downregulated exosomal proteins. Exosomes derived from the crystal-interacting macrophages induced migration/activation of monocytes and activated phagocytic activity of the macrophages. Knockdown of vimentin by siRNA successfully suppressed such effects of the exosomes derived from COM crystal-exposed macrophages. |
| 2018 | Singhto N, et al. [46] | Cell: Human macrophages (exosomes) Crystal: 100 µg/mL COM Incubation: 24 h |
nanoLC-ESI-Qq-TOF, cell-migration assay, crystal-binding assay, crystal-migration assay | 7 upregulated and 19 downregulated exosomal proteins. Exosomes derived from the crystal-interacting macrophages induced neutrophil migration, enhanced production of a pro-inflammatory cytokine IL-8 from renal tubular cells, had greater binding capability to COM crystals, and activated crystal invasion through ECM. |