Chronic Low Dose Rate Ionizing Radiation Exposure Induces Premature Senescence in Human Fibroblasts that Correlates with Up Regulation of Proteins Involved in Protection against Oxidative Stress
Abstract
:1. Introduction
2. Experimental
2.1. Radiation Source
2.2. Cell Culture Condition and Cell Growth Kinetics
2.3. Senescence-Associated β-Galactosidase (SA-βgal) Assay
2.4. Western Blot Analysis
2.5. Two-Dimensional Polyacrylamide Gel Electrophoresis (2DE)
2.6. MALDI-TOF Mass Spectrometry Analysis and Protein Identification
2.7. Heatmap and Hierarchical Clustering
3. Results and Discussion
3.1. Radiation-Induced Senescence in Normal Human Fibroblasts
3.2. Effect of Ionizing Radiation on Fibroblast Proteome
Spot Number | Protein Name | Protein ID | Theoretical pI | Theoretical Mr, kDa | Peptide Matches | Sequence Coverage % | Mascot Score | Protein Function |
---|---|---|---|---|---|---|---|---|
1 | α-Enolase | P06733 | 7.0 | 47.2 | 15 | 36 | 120 | Glycolysis |
2 | α-Enolase | P06733 | 7.0 | 47.2 | 20 | 33 | 197 | Glycolysis |
3 | Proliferation-associated protein 2G4 | Q9UQ80 | 6.1 | 43.8 | 14 | 27 | 66 | Involved in cell cycle arrest/cell proliferation |
4 | 26S protease regulatory subunit 8 | P62195 | 7.1 | 45.6 | 12 | 36 | 85 | Proteasome complex |
5 | Mannose-6-phosphate receptor-binding protein 1 | O60664 | 5.8 | 28.1 | 15 | 48 | 141 | Vesicle-mediated transport |
6 | Serine-threonine kinase receptor-associated protein | Q9Y3F4 | 5.0 | 38.4 | 9 | 41 | 70 | mRNA processing, regulator of TGFβ pathway, cofactor of p53 |
7 | Serine-threonine kinase receptor-associated protein | Q9Y3F4 | 5.0 | 38.4 | 8 | 32 | 65 | mRNA processing, regulator of TGFβ pathway, cofactor of p53 |
8 | Alcohol dehydrogenase | P14550 | 6.3 | 36.6 | 13 | 55 | 110 | Glucose metabolic process |
9 | LIM and SH3 domain protein 1 | Q14847 | 6.4 | 30.1 | 10 | 31 | 75 | Actin-binding protein |
10 | Eukaryotic translation initiation factor 3 | Q13347 | 5.4 | 36.5 | 9 | 30 | 71 | Protein biosynthesis |
11 | Eukaryotic translation initiation factor 3 | Q13347 | 5.4 | 36.5 | 10 | 32 | 73 | Protein biosynthesis |
12 | F-actin-capping protein α-1 | P52907 | 5.4 | 32.9 | 14 | 67 | 172 | Regulation of cell motility |
13 | Tubulin beta | P07437 | 4.8 | 48.7 | 14 | 45 | 132 | Cytoskeleton |
14 | Annexin A1 | P04083 | 6.6 | 38.7 | 18 | 52 | 179 | Regulation of apoptosis |
15 | Annexin A1 | P04083 | 6.6 | 38.7 | 19 | 62 | 202 | Regulation of apoptosis |
16 | PDZ and LIM domain protein 1 | O00151 | 6.6 | 36.5 | 9 | 23 | 78 | Cytoskeleton protein required for actin stress fiber formation |
17 | F-actin-capping protein subunit β | P47756 | 5.4 | 31.5 | 9 | 44 | 67 | Actin-binding protein |
18 | Chloride intracellular channel protein CLIP1 | O00299 | 5.1 | 27.4 | 16 | 70 | 183 | Chloride ion channel, anti-apoptotic |
19 | Annexin A2 | P07355 | 7.6 | 38.6 | 20 | 51 | 210 | Stress response, regulation of apoptosis |
20 | Glutathione transferase omega-1 | P78417 | 6.2 | 27.8 | 10 | 29 | 100 | Metabolism of xenobiotics, antioxidant |
21 | Heat shock protein β-1 (Hsp27) | P04792 | 6.0 | 22.8 | 8 | 38 | 65 | Involved in stress resistance and actin organization |
22 | Phosphoglycerate mutase | P18669 | 6.4 | 26.7 | 18 | 73 | 200 | Glycolysis |
23 | Ubiquitin thiolesterase L1, acidic isoforms | P09936 | 5.3 | 24.8 | 14 | 72 | 131 | Processing of ubiquitinated proteins; anti-apoptotic |
24 | Ubiquitin thiolesterase L1, basic isoforms | P09936 | 5.3 | 24.8 | 14 | 75 | 171 | Processing of ubiquitinated proteins; anti-apoptotic |
25 | Peroxiredoxin 6 | P30041 | 6.0 | 25.0 | 7 | 36 | 57 | Antioxidant |
26 | Peroxiredoxin 6 | P30041 | 6.0 | 25.0 | 13 | 64 | 144 | Antioxidant |
27 | Peroxiredoxin 6 | P30041 | 6.0 | 25.0 | 14 | 70 | 155 | Antioxidant |
28 | Triosephosphate isomerase | P60174 | 6.4 | 26.7 | 15 | 58 | 177 | Carbohydrate metabolism |
29 | 26S proteasome subunit 10 | O75832 | 5.4 | 20.4 | 8 | 49 | 58 | Acts as a regulatory subunit of the 26S proteasome |
30 | Glutathione S-transferase P | P09211 | 5.4 | 23.6 | 9 | 48 | 94 | Antioxidant, anti-apoptotic |
31 | Glutathione S-transferase P | P09211 | 5.4 | 23.6 | 10 | 56 | 146 | Antioxidant, anti-apoptotic |
32 | Protein DJ-1 | Q99497 | 6.3 | 19.9 | 8 | 43 | 60 | Redox-sensitive chaperone and a sensor for oxidative stress |
33 | Proteasome subunit α type-2 | P25787 | 6.9 | 26.0 | 8 | 44 | 70 | Proteasome complex |
34 | Acyl-protein thioesterase 1 | O75608 | 6.3 | 26.7 | 5 | 41 | 56 | De-palmitoylation of signaling proteins |
35 | Superoxide dismutase Mn SOD2 | P04179 | 8.3 | 24.7 | 7 | 36 | 69 | Antioxidant, age-dependent response to ROS |
36 | Superoxide dismutase Mn SOD2 | P04179 | 8.3 | 24.7 | 8 | 40 | 78 | Antioxidant, age-dependent response to ROS |
37 | Peroxiredoxin-2 | P32119 | 5.7 | 21.9 | 9 | 35 | 79 | Antioxidant, anti-apoptotic |
38 | Adenine phosphoribosyltransferase | P07741 | 5.8 | 19.6 | 8 | 68 | 91 | Nucleotide metabolism |
39 | Nucleoside diphosphate kinase A | P15531 | 5.8 | 17.3 | 8 | 61 | 90 | Synthesis of nucleoside triphosphates other than ATP, tumor suppressor, cofactor of p53 |
40 | Transgelin | Q01995 | 8.9 | 22.6 | 13 | 56 | 121 | Actin-binding protein, senescence marker |
3.3. Radiation Induced Stress Response
4. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Loseva, O.; Shubbar, E.; Haghdoost, S.; Evers, B.; Helleday, T.; Harms-Ringdahl, M. Chronic Low Dose Rate Ionizing Radiation Exposure Induces Premature Senescence in Human Fibroblasts that Correlates with Up Regulation of Proteins Involved in Protection against Oxidative Stress. Proteomes 2014, 2, 341-362. https://doi.org/10.3390/proteomes2030341
Loseva O, Shubbar E, Haghdoost S, Evers B, Helleday T, Harms-Ringdahl M. Chronic Low Dose Rate Ionizing Radiation Exposure Induces Premature Senescence in Human Fibroblasts that Correlates with Up Regulation of Proteins Involved in Protection against Oxidative Stress. Proteomes. 2014; 2(3):341-362. https://doi.org/10.3390/proteomes2030341
Chicago/Turabian StyleLoseva, Olga, Emman Shubbar, Siamak Haghdoost, Bastiaan Evers, Thomas Helleday, and Mats Harms-Ringdahl. 2014. "Chronic Low Dose Rate Ionizing Radiation Exposure Induces Premature Senescence in Human Fibroblasts that Correlates with Up Regulation of Proteins Involved in Protection against Oxidative Stress" Proteomes 2, no. 3: 341-362. https://doi.org/10.3390/proteomes2030341
APA StyleLoseva, O., Shubbar, E., Haghdoost, S., Evers, B., Helleday, T., & Harms-Ringdahl, M. (2014). Chronic Low Dose Rate Ionizing Radiation Exposure Induces Premature Senescence in Human Fibroblasts that Correlates with Up Regulation of Proteins Involved in Protection against Oxidative Stress. Proteomes, 2(3), 341-362. https://doi.org/10.3390/proteomes2030341