Table 1. Genes whose expression was increased in RASMC subjected to Na+,K+-ATPase inhibition.
| Gene symbol//gene title (ref #) – functional categories | K+-free medium | ouabain | ||
| Fold change | p value | Fold change | p value | |
| Gdf15//growth differentiation factor 15 (D) - D | 15.17 | 1.88E-06 | 7.44 | 6.03E-06 |
| Ereg//epiregulin (1) – D | 15.14 | 1.59E-06 | 9.63 | 4.10E-06 |
| Cyp1a1//cytochrome P450, family 1, subfamily a (15) - O | 14.22 | 1.59E-06 | 15.58 | 2.95E-06 |
| Fos//FBJ osteosarcoma oncogene (427) – T | 7.91 | 2.23E-05 | 3.95 | 1.23E-04 |
| Atf3//activating transcription factor (27) – T | 7.83 | 2.85E-05 | 4.53 | 1.07E-04 |
| Slc9a3//solute carrier family 9 (sodium/hydrogen exchang – O | 7.52 | 2.13E-06 | 3.25 | 1.22E-05 |
| Nppc//natriuretic peptide C – O | 7.42 | 6.35E-06 | 6.80 | 9.53E-06 |
| Bhlhe41//basic helix-loop-helix family, member e41 – T | 7.42 | 6.59E-06 | 6.23 | 1.13E-05 |
| Klf10//Kruppel-like factor 10 (2) – T | 7.16 | 4.32E-06 | 4.09 | 1.38E-05 |
| Trib1//Tribbles homolog 1 (Drosophila) (2) – D | 7.09 | 1.50E-06 | 4.47 | 4.54E-06 |
| Il6r//interleukin 6 receptor (1) – I | 6.71 | 9.08E-07 | 4.37 | 3.17E-06 |
| Ets2//v-ets erythroblastosis virus E26 oncogene homolog 2– T | 6.68 | 4.93E-06 | 5.35 | 9.09E-06 |
| Fam43a//family with sequence similarity 43, member A – U | 6.56 | 6.89E-06 | 3.45 | 3.34E-05 |
| Arrdc4//arrestin domain containing 4– U | 5.89 | 1.70E-06 | 3.06 | 7.44E-06 |
| Tppp//tubulin polymerization promoting protein – D | 5.89 | 1.11E-05 | 3.58 | 4.18E-05 |
| Ptgs2//prostaglandin-endoperoxide synthase 2 (588) – I | 5.68 | 1.44E-06 | 3.71 | 4.45E-06 |
| F3//coagulation factor III (thromboplastin, tissue factor I | 5.64 | 1.62E-06 | 3.39 | 5.50E-06 |
| Enc1//ectodermal-neural cortex – D | 5.61 | 9.08E-07 | 3.85 | 2.57E-06 |
| Mmp28//matrix metallopeptidase 28– I | 5.47 | 3.64E-06 | 4.24 | 7.44E-06 |
| Epha2//Eph receptor A2 (3) – D | 5.46 | 2.73E-06 | 3.32 | 8.72E-06 |
| RGD1307396//similar to RIKEN cDNA 6330406I15 – U | 5.39 | 2.12E-06 | 3.94 | 5.19E-06 |
| Slc25a25//solute carrier family 25 (mitochondrial Pi carrier) – O | 5.04 | 2.66E-06 | 2.85 | 1.12E-05 |
| Nr4a1//nuclear receptor subfamily 4, group A (14) – T | 4.99 | 9.44E-06 | 4.67 | 1.33E-05 |
| Per2//period homolog 2 (Drosophila) (6) – O | 4.88 | 7.48E-06 | 5.47 | 8.33E-06 |
| Zbtb2//zinc finger and BTB domain containing 2– T | 4.68 | 2.63E-06 | 3.09 | 8.01E-06 |
| Rab32//RAB32, member RAS oncogene family – T | 4.68 | 1.49E-06 | 2.51 | 7.26E-06 |
| Isg20//interferon stimulated exonuclease gene 20– I | 4.67 | 2.44E-06 | 4.71 | 4.06E-06 |
| Hbegf//heparin-binding EGF-like growth factor (4) – D | 4.65 | 2.60E-06 | 2.69 | 1.10E-05 |
| Pde4b//phosphodiesterase 4B, cAMP-specific – O | 4.52 | 3.64E-06 | 2.43 | 2.15E-05 |
| Csrnp1//cysteine-serine-rich nuclear protein 1–D | 4.52 | 3.63E-06 | 3.52 | 7.73E-06 |
| PVR//poliovirus receptor - D | 4.50 | 3.47E-06 | 3.58 | 7.26E-06 |
| Hes1//hairy and enhancer of split 1 (Drosophila) (34) – T | 4.47 | 5.68E-06 | 2.94 | 1.93E-05 |
| Bcl6//B-cell CLL/lymphoma 6 (1) –D | 4.45 | 2.12E-06 | 2.90 | 7.26E-06 |
| Ier5//immediate early response 5-T | 4.45 | 5.59E-06 | 2.76 | 2.26E-05 |
| Sgk1//serum/glucocorticoid regulated kinase 1 (14) - O | 4.42 | 3.96E-06 | 3.64 | 7.69E-06 |
| Plk3//polo-like kinase 3 (20) -D | 4.41 | 1.03E-05 | 3.13 | 3.05E-05 |
| Klf5//Kruppel-like factor 5-T | 4.39 | 1.17E-05 | 3.43 | 2.64E-05 |
| Mthfd2l//methylenetetrahydrofolate dehydrogenase – O | 4.38 | 9.85E-06 | 2.49 | 6.04E-05 |
| Areg//amphiregulin (3) – D | 4.37 | 1.00E-05 | 3.26 | 2.51E-05 |
| RGD1563891//similar to core 2 beta-1,6-N-acetylglucosam – U | 4.36 | 5.54E-05 | 3.52 | 1.17E-04 |
| Fst//follistatin (9) – D | 4.35 | 6.59E-06 | 5.50 | 6.34E-06 |
| Fosl1//fos-like antigen 1-T | 4.27 | 1.20E-05 | 3.41 | 2.59E-05 |
| Ier2//immediate early response 2 (1) – T | 4.24 | 2.62E-05 | 1.99 | 6.15E-04 |
| Baiap2//BAI1-associated protein 2-D | 4.14 | 9.08E-07 | 3.98 | 2.57E-06 |
| Rassf9//Ras association (RalGDS/AF-6) domain family – D | 4.12 | 2.41E-06 | 2.86 | 7.26E-06 |
| Chka//choline kinase alpha – O | 4.10 | 1.82E-06 | 4.71 | 2.95E-06 |
| Irf2bpl//interferon regulatory factor 2-binding protein-like – I | 4.10 | 3.37E-05 | 3.27 | 7.69E-05 |
| Mum1l1//melanoma-associated antigen (mutated) 1-like 1–I | 4.00 | 4.60E-06 | 2.69 | 1.53E-05 |
| Nr4a3//nuclear receptor subfamily 4, group A, mem 3 (5) – T | 3.99 | 1.00E-05 | 4.13 | 1.19E-05 |
| Tas2r135//taste receptor, type 2, member 135–O | 3.94 | 3.86E-05 | 3.56 | 6.11E-05 |
| Errfi1//ERBB receptor feedback inhibitor 1–D | 3.93 | 4.30E-06 | 2.82 | 1.19E-05 |
| Skil//SKI-like oncogene - T | 3.92 | 9.08E-07 | 2.13 | 6.03E-06 |
| Zswim4//zinc finger, SWIM-type containing 4–T | 3.92 | 2.09E-06 | 2.31 | 1.02E-05 |
| Dusp10//dual specificity phosphatase 10 (3)-D | 3.92 | 8.95E-06 | 2.09 | 8.82E-05 |
| Has2//hyaluronan synthase 2 (3) –I | 3.91 | 9.85E-06 | 7.60 | 4.67E-06 |
| Txnip//thioredoxin interacting protein (9) – I | 3.88 | 1.82E-06 | 2.31 | 8.58E-06 |
| Mdm2//Mdm2 p53 binding protein homolog (mouse) (22) – T | 3.85 | 9.08E-07 | 2.98 | 2.95E-06 |
| Fam171b//family with sequence similarity 171, member B – U | 3.84 | 3.05E-06 | 4.82 | 3.26E-06 |
| Stk17b//serine/threonine kinase 17b –O | 3.76 | 3.65E-06 | 4.00 | 4.67E-06 |
| Zfp36//zinc finger protein 36–T | 3.70 | 6.56E-05 | 2.15 | 7.25E-04 |
| Rab20//RAB20, member RAS oncogene family –I | 3.66 | 4.53E-06 | 3.90 | 5.52E-06 |
| Pnrc1//proline-rich nuclear receptor coactivator 1–T | 3.66 | 2.19E-07 | 3.10 | 7.72E-07 |
| Abcb1b//ATP-binding cassette, subfamily B, mem 1B (3) – O | 3.65 | 9.08E-07 | 2.72 | 3.17E-06 |
| Smad3//SMAD family member 3 (20) –T | 3.64 | 4.27E-06 | 2.78 | 1.04E-05 |
| RGD1306119//similar to transcriptional regulating prot 132 – T | 3.59 | 1.13E-05 | 1.80 | 2.42E-04 |
| Htr2a//5-hydroxytryptamine (serotonin) receptor 2A (1) – O | 3.58 | 9.08E-07 | 3.10 | 2.78E-06 |
| Jun//jun proto-oncogene (799) –T | 3.57 | 1.77E-06 | 2.76 | 4.54E-06 |
| Zfat//zinc finger and AT hook domain containing – T | 3.57 | 4.59E-06 | 3.01 | 8.69E-06 |
| Dusp6//dual specificity phosphatase 6 (2) -O | 3.56 | 4.79E-06 | 2.42 | 1.73E-05 |
| Ier5l//immediate early response 5-like T | 3.55 | 4.98E-06 | 2.71 | 1.29E-05 |
| Bmp2//bone morphogenetic protein 2 (13) –D | 3.52 | 3.96E-05 | 3.69 | 4.14E-05 |
| Gnat1//guanine nucleotide-binding protein, alpha t –O | 3.50 | 2.44E-06 | 3.86 | 3.26E-06 |
| RGD1305254//similar to transmembrane protein 2–U | 3.48 | 3.31E-05 | 2.14 | 2.69E-04 |
| Alkbh//alkB, alkylation repair homolog (E. coli) –D | 3.45 | 2.26E-06 | 2.44 | 7.40E-06 |
| Klf4//Kruppel-like factor 4 (gut) (5) –T | 3.44 | 1.54E-05 | 2.49 | 5.57E-05 |
| Hapln3//hyaluronan and proteoglycan link protein 3 – O | 3.44 | 2.58E-05 | 1.95 | 3.45E-04 |
| Mafk//v-maf musculoaponeurotic fibrosarcoma onco hom K–T | 3.42 | 8.48E-06 | 2.75 | 1.91E-05 |
| Maff//v-maf musculoaponeurotic fibrosarcoma onco hom F-T | 3.42 | 2.09E-05 | 2.55 | 6.83E-05 |
| Dusp16//dual specificity phosphatase 16 (2) –O | 3.39 | 1.94E-05 | 2.23 | 1.10E-04 |
| Gprc5a//G protein-coupled receptor, family C, gr 5, mem A–O | 3.38 | 3.26E-05 | 4.73 | 1.74E-05 |
| Lgr5//leucine-rich repeat contain G protein coupled recept –O | 3.32 | 1.11E-05 | 4.12 | 8.86E-06 |
| Per1//period homolog 1 (Drosophila) (4) –O | 3.32 | 5.54E-06 | 4.09 | 5.06E-06 |
| Cd80//Cd80 molecule (28) –I | 3.30 | 6.40E-06 | 2.10 | 3.72E-05 |
| Mybl1//myeloblastosis oncogene-like 1 (1) –T | 3.29 | 1.86E-05 | 2.03 | 1.55E-04 |
| Pim1//pim-1 oncogene (5) –D | 3.27 | 6.86E-06 | 1.84 | 8.03E-05 |
| Osmr//oncostatin M receptor –I | 3.25 | 2.76E-05 | 2.00 | 2.57E-04 |
| Smad7//SMAD family member 7 (6) –D | 3.23 | 4.22E-06 | 2.05 | 2.23E-05 |
| Cpeb4//cytoplasmic polyadenyl element bind prot 4 (1) –T | 3.20 | 4.79E-06 | 3.01 | 7.42E-06 |
| Aen//apoptosis-enhancing nuclease (5) D | 3.17 | 5.96E-06 | 3.10 | 8.39E-06 |
| Nr4a2//nuclear receptor subfamily 4, group A, mem 2 (4) – T | 3.16 | 1.56E-05 | 3.99 | 1.15E-05 |
| Tnfrsf1b//tumor necrosis factor receptor superfamily –D | 3.15 | 2.67E-05 | 1.99 | 2.31E-04 |
| Lhfpl2//lipoma HMGIC fusion partner-like 2–O | 3.10 | 4.60E-06 | 1.76 | 5.10E-05 |
| Rap2b//RAP2B, member of RAS oncogene family –O | 3.07 | 1.00E-05 | 2.34 | 3.03E-05 |
| Lmbrd2//LMBR1 domain containing 2–U | 3.07 | 9.85E-06 | 2.70 | 1.77E-05 |
| Cdc42ep1//CDC42 effector protein (Rho GTPase binding) 1 – D | 3.06 | 2.92E-05 | 2.80 | 4.71E-05 |
| Kdm6b//lysine (K)-specific demethylase 6B –T | 3.04 | 7.50E-06 | 2.04 | 3.94E-05 |
| RGD1310794//similar to RIKEN cDNA C030048B08 - D | 3.04 | 2.47E-04 | 4.01 | 1.07E-04 |
| Sertad2//SERTA domain containing 2-T | 3.03 | 1.40E-05 | 2.55 | 3.05E-05 |
RASMC were treated with 3 mM ouabain or K+-free medium for 6 hr. Listed are assigned genes whose expression was increased in K+-free medium by more than 3-fold and was different by less than 2-fold in the presence of ouabain compared to K+-free medium. GeneChip expression analysis was performed as described in the Methods section. mRNA content in control cells was taken as 1.00. Genes whose expression is altered in ischemia/hypoxia are shown in bold. Appearing in parentheses are numbers of citations in PubMed. Listed in italics are genes whose differential expression was detected in ischemic tissue by whole genome microarray-based analysis [12]–[18]. Data on gene function from GeneCards database (www.genecards.org) were used for identification of gene function. Functional categories: T– regulators of transcription/translation, RNA processing and degradation; D– regulators of cell adhesion, migration, proliferation, differentiation and death; I– inflammation and immune responses; O– others; U– unknown function.