Table 2. Biological pathways significantly modulated by nicotine in SH-SY5Y cellsa.
| Pathway | p value | FDRb | Genes significantly regulated by nicotine |
|---|---|---|---|
| Glucocorticoid receptor signaling | 3.11 × 10−7 | 1.77 × 10−4 | AGT, AR, BCL2, CD3G, DUSP1, FGG, FOS, GTF2H2, IKKγ, JAK3, MAP3 K7IP1, MAPK14, MED14, NFATC3, PIK3CG, SMAD2, STAT5A, TGFB2, TGFBR2, TRAF6, YWHAH |
| p38 MAPK signaling | 2.40 × 10−6 | 6.82 × 10−4 | ATF2, DAXX, DUSP1, HMGN1, IRAK3, MAP3K7IP1, MAPK14, MEF2D, PLA2G4A, TGFB2, TGFBR2, TRAF6 |
| PI3K/AKT signaling | 9.55 × 10−6 | 1.81 × 10−3 | BCL2, EIF4EBP1, FOXO1, IKKγ, ITGB1, JAK3, PIK3CG, PPM1L, RPS6KB1, SFN, TRP53, YWHAH |
| PTEN signaling | 5.01 × 10−5 | 7.13 × 10−3 | BCL2, BCL2L11, CDC42, FOXO1, IKKγ, ITGB1, NGFR, PIK3CG, RPS6KB1, YWHAH |
| Acute-phase response signaling | 1.02 × 10−4 | 0.012 | AGT, APOA1, FGG, FOS, IKKγ, IL6R, IL6ST, MAP3K7IP1, MAPK14, NGFR, PIK3CG, TF, TRAF6 |
| ERK/MAPK signaling | 1.70 × 10−4 | 0.015 | ARAF, ATF2, DUSP1, EIF4EBP1, FOS, ITGB1, PIK3CG, PLA2G4A, PPM1L, PPP1CA, RAPGEF3, YWHAH |
| Mitochondrial dysfunction | 2.09 × 10−4 | 0.015 | COX6B1, COX7B, COX7C, NDUFA4, NDUFV1, OGDH, SDHB, SDHC, SNCA, UQCRFS1 |
| VEGF signaling | 2.14 × 10−4 | 0.015 | BCL2, EIF2B1, EIF2B5, FOXO1, PIK3CG, SFN, VCL, VEGFA |
| Toll-like receptor signaling | 2.57 × 10−4 | 0.015 | FOS, IKKγ, IRAK3, MAP3K7IP1, MAP4K4, MAPK14, TRAF6 |
| PPAR signaling | 2.75 × 10−4 | 0.015 | FOS, IKKγ, MAP3K7IP1, MAP4K4, NGFR, NR2F1, STAT5A, TRAF6 |
| IL-6 signaling | 2.95 × 10−4 | 0.015 | FOS, IKKγ, IL6R, IL6ST, MAP3K7IP1, MAP4K4, MAPK14, NGFR, TRAF6 |
| T-cell receptor signaling | 5.13 × 10−4 | 0.024 | CALM2, CD3G, CSK, FOS, IKKγ, NFATC3, PIK3CG, ZAP70 |
| Hepatic fibrosis/hepatic stellate cell activation | 7.24 × 10−4 | 0.032 | AGT, BCL2, IGF1R, IL6R, NGFR, SMAD2, TGFB2, TGFBR2, VEGFA |
| Death receptor signaling | 8.71 × 10−4 | 0.035 | BCL2, FLIP, DAXX, IKKγ, MAP4K4, TNFRSF10B |
a
The pathways and genes included in each pathway were based on the output of Ingenuity Pathway Analysis (IPA; http://www.ingenuity.com/). Some pathways may be partially overlapped with others. No action was taken to remove any possible redundancy
b
The FDR values were computed based on the p values of the pathways included in the IPA output via the method of Benjamini and Hochberg (1995). Pathways with FDR <0.05 are included in Table 2