Table 5.
Effect of PFOS on upstream regulators of the proteomic response
| Upstream Regulator | Name | Function | Activation Z-score | Target Molecules in Data Set | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
|
|
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| SD +PFOS | H-SD +PFOS | HFD +PFOS | PFOS treatment | SD +PFOS | SD & H-SD +PFOS | H-SD +PFOS | H-SD & HFD +PFOS | HFD +PFOS | |||
|
| |||||||||||
| Ppar-α | peroxisome proliferator activated receptor alpha | lipid metabolism in the liver | 2.306 | 2.864 | 2.974 | Acot1 Acsl1 Aldh3a2 Cyp2b6 Cyp2c8 Cyp4a11 Cyp4a14 Ehhadh Hsd17b11 Slc27a2 | Aldob Pklr | Csad | Acox1 Cps1 Eci1 | Acaa1b, Cyp2c54, Hsd17b4, Por | Dec1 Cat Decr2 |
|
| |||||||||||
| Lep | leptin | adipokine, pro-inflammatory cytokine | 2.828 | 3.162 | 2.530 | Cyb5a Cyp2a12/Cyp2a22 Cyp2c8 Cyp3a5 Cyp4a11 Cyp4a14 Ehhadh | Aldob | Acox1 Cps1 | Cyp2c54, Gstm3 | Fmo5 | |
|
| |||||||||||
| Nr1i3 | Car, nuclear receptor subfamily 1 group I member 3 | xenobiotic and endobiotic metabolism | 2.583 | 2.946 | 2.771 | Ces2a Ces2c Cyp2b6 Cyp2c8 Cyp3a5 Ephx1 | Ugt2b28 | Cyp2a6 | Aldh1a1 Ugt1a1 | Gstm3, Gstm5, Por | |
|
| |||||||||||
| Cftr | cystic fibrosis transmembrane conductance regulator | involved in AMPK signaling | 2.213 | 2.804 | 2.804 | Cyp2b6 Cyp3a5 Cyp4a11 Hsd17b11 Slc27a2 | Acaa1b, Hsd17b4, Por | ||||
|
| |||||||||||
| Abcb6 | ATP binding cassette subfamily B member 6 | transporter, involved in mitochondrial function | 2.201 | 2.418 | 2.202 | Cyp2a12/Cyp2a22 Cyp2b6 Cyp3a5 Cyp4a11 | Cyp2a6 | Cyp2c54 | |||
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| |||||||||||
| Smarcb1 | actin dependent regulator of chromatin, subfamily b, member 1 | involved in AMPK signaling | 2.000 | 2.236 | 2.236 | Acsl1 Cyp2c8 Cyp4a11 Cyp4a14 | Cyp2c54 | ||||
|
| |||||||||||
| Tcf7l2 | transcription factor 7 like 2 | Wnt signaling and blood glucose homeostasis | 2.236 | 2.000 | 2.000 | Acsl1 Aldg3a2 Cyp2c8 Ehhadh Slc27a2 | Entpd5 | ||||
|
| |||||||||||
| Nrf2 | nuclear factor, erythroid 2 like 2 | antioxidant and detoxification response | N/A | 2.383 | 2.070 | Akr1a1 Ces1g Ugt1a1 | Cyp2a12/Cyp2a22, Cyp4a14, Cyp4a22, Ephx1, Gstm3, Gstm5 |
Cat Dstn Hacd3 Inmt |
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|
| |||||||||||
| Nr1i2 | PXR, nuclear receptor subfamily 1 group I member 2 | xenobiotic and endobiotic metabolism | N/A | 2.218 | 2.218 | Acox1 Ald1a1 Ugt1a1 | Ces2a, Cyp2b6, Cyp3a6, Gstm3, Gstm5, Por |
Cat | |||
Protein data were analyzed using Perseus open source software. The numbers of significantly increased and decreased proteins for relevant comparisons were calculated. (student’s t-test, p-value ≤ 0.05, false discovery rate (FDR) < 0.05). Comparisons were SD/SD+PFOS, H-SD/H-SD+PFOS, and HFD/HFD+PFOS. Differentially expressed proteins among all comparisons were further analyzed using Ingenuity Pathway Analysis (IPA)’s upstream analysis. Significant upstream regulatory molecules are described for PFOS treatment in each diet. For each comparison, an activation z-score was calculated to predict activation of upstream regulators. A positive z-score indicates upregulation and a negative z-score indicates downregulation.