Impact of the antiproliferative agent ciclopirox olamine treatment on stem cells proteome

doi:10.4252/wjsc.v5.i1.9

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Jan 26, 2013 (publication date) through Apr 25, 2024

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World Journal of Stem Cells

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1948-0210

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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World J Stem Cells. Jan 26, 2013; 5(1): 9-25
Published online Jan 26, 2013. doi: 10.4252/wjsc.v5.i1.9

Table 1 Non-redundant proteins

Protein name	Gene name	Swiss-prot	Nominal mass	CPI	PMF-score	PMF sequence coverage	MS/MS-score	MS/MS-sequence coverage
Low molecular weight phosphotyrosine protein phosphatase	Acp1	PPAC_MOUSE	18 636	6.4	96	65	80	24
Actin, cytoplasmic 1	Actb	ACTB_MOUSE	42 052	5.2	170	70	312	15
Aminoacylase-1	Acy1	ACY1_MOUSE	45 980	5.9	167	56	44	5
Aldose reductase	Akr1b1	ALDR_MOUSE	36 052	6.9	128	43	136	10
Aldehyde dehydrogenase, mitochondrial	Aldh2	ALDH2_MOUSE	57 015	8.6	221	54	131	7
Annexin A3	Anxa3	ANXA3_MOUSE	36 520	5.2	84	47	111	14
Adenine phosphoribosyltransferase	Aprt	APT_MOUSE	19 883	6.4	88	67	216	27
Rho GDP-dissociation inhibitor 1	Arhgdia	GDIR1_MOUSE	23 450	5	123	54	66	11
ATP synthase subunit α, mitochondrial	Atp5a1	ATPA_MOUSE	59 830	9.7	100	28	53	4
ATP synthase subunit β, mitochondrial	Atp5b	ATPB_MOUSE	56 265	5.1	90	30	167	10
ATP synthase subunit d, mitochondrial	Atp5h	ATP5H_MOUSE	18 795	5.4	122	70	169	36
F-actin-capping protein subunit α-2	Capza2	CAZA2_MOUSE	33 118	5.5	148	69	19	9
F-actin-capping protein subunit β	Capzb	CAPZB_MOUSE	31 611	5.4	117	61	129	8
Chromobox protein homolog 3	Cbx3	CBX3_MOUSE	21 013	5	38	36	67	6
T-complex protein 1 subunit β	Cct2	TCPB_MOUSE	57 783	6	248	61	75	9
T-complex protein 1 subunit epsilon	Cct5	TCPE_MOUSE	60 042	5.7	186	60	138	6
Cofilin-1	Cfl1	COF1_MOUSE	18 776	9.1	95	45	87	13
UMP-CMP kinase	Cmpk1	KCY_MOUSE	22 379	5.6	74	52	29	10
Coactosin-like protein	Cotl1	COTL1_MOUSE	16 048	5.1	86	60	116	14
Cathepsin D	Ctsd	CATD_MOUSE	45 381	6.9	160	41	95	4
Dihydrolipoyl dehydrogenase, mitochondrial	Dld	DLDH_MOUSE	54 751	9	112	48	81	2
Elongation factor 1-α1	Eef1a1	EF1A1_MOUSE	50 424	9.7	68	34	115	8
Elongation factor 1-δ	Eef1d	EF1D_MOUSE	31 388	4.8	86	54	79	9
Elongation factor 2	Eef2	EF2_MOUSE	96 222	6.4	52	26	29	1
Eukaryotic translation initiation factor 3 subunit F	Eif3f	EIF3F_MOUSE	38 090	5.2	109	45	106	14
Eukaryotic translation initiation factor 3 subunit G	Eif3g	EIF3G_MOUSE	35 901	5.6	54	35	23	7
Eukaryotic translation initiation factor 3 subunit I	Eif3i	EIF3I_MOUSE	36 837	5.3	228	78	89	16
Eukaryotic translation initiation factor 4H	Eif4h	IF4H_MOUSE	27 381	7.5	83	51	65	8
Eukaryotic translation initiation factor 5A-1	Eif5a	IF5A1_MOUSE	17 049	4.9	115	58	170	22
α-enolase	Eno1	ENOA_MOUSE	47 453	6.4	183	64	170	13
Electron transfer flavoprotein subunit α, mitochondrial	Etfa	ETFA_MOUSE	35 330	9.5	138	59	100	9
Fatty acid-binding protein, heart	Fabp3	FABPH_MOUSE	14 810	6.1	86	77	212	39
Peptidyl-prolyl cis-trans isomerase FKBP4	Fkbp4	FKBP4_MOUSE	51 939	5.4	122	38	168	9
Fascin	Fscn1	FSCN1_MOUSE	55 215	6.5	129	45	26	6
Glyceraldehyde-3-phosphate dehydrogenase	Gapdh	G3P_MOUSE	36 072	9.2	62	38	40	8
Lactoylglutathione lyase	Glo1	LGUL_MOUSE	20 967	5.1	134	66	114	20
Glyoxalase domain-containing protein 4	Glod4	GLOD4_MOUSE	33 581	5.2	167	69	115	13
Glutamate dehydrogenase 1, mitochondrial	Glud1	DHE3_MOUSE	61 640	8.8	70	37	60	5
Guanine nucleotide-binding protein subunit β-2-like 1	Gnb2l1	GBLP_MOUSE	35 511	8.9	116	55	20	5
Growth factor receptor-bound protein 2	Grb2	GRB2_MOUSE	25 336	5.9	73	54	36	17
Histone H2B type 1-B	Hist1h2bb	H2B1B_MOUSE	13 944	10.8	52	41	93	19
Histone H2A type 2-C	Hist2h2ac	H2A2C_MOUSE	13 980	11.4	50	55	67	12
Heterogeneous nuclear ribonucleoprotein A/B	Hnrnpab	ROAA_MOUSE	30 926	8.7	83	30	107	5
Heterogeneous nuclear ribonucleoproteins C1/C2	Hnrnpc	HNRPC_MOUSE	34 421	4.8	57	32	57	6
Heterogeneous nuclear ribonucleoprotein F	Hnrnpf	HNRPF_MOUSE	46 043	5.2	163	56	207	12
Heterogeneous nuclear ribonucleoprotein H	Hnrnph1	HNRH1_MOUSE	49 454	5.9	166	61	134	15
Heterogeneous nuclear ribonucleoprotein K	Hnrnpk	HNRPK_MOUSE	51 230	5.3	144	46	251	11
Heat shock protein HSP 90-α	Hsp90aa1	HS90A_MOUSE	85 134	4.8	131	31	130	5
Heat shock protein HSP 90-β	Hsp90ab1	HS90B_MOUSE	83 615	4.8	62	25	78	6
Heat shock 70 kDa protein 4	Hspa4	HSP74_MOUSE	94 872	5	242	54	102	3
78 kDa glucose-regulated protein	Hspa5	GRP78_MOUSE	72 492	4.9	78	25	122	5
Heat shock cognate 71 kDa protein	Hspa8	HSP7C_MOUSE	71 055	5.2	234	58	154	4
Stress-70 protein, mitochondrial	Hspa9	GRP75_MOUSE	73 768	5.8	219	50	272	7
Heat shock protein β-1	Hspb1	HSPB1_MOUSE	23 057	6.1	144	55	344	24
60 kDa heat shock protein, mitochondrial	Hspd1	CH60_MOUSE	61 088	5.8	334	69	232	10
Isocitrate dehydrogenase (NAD) subunit α, mitochondrial	Idh3a	IDH3A_MOUSE	40 069	6.3	70	31	158	12
Inosine-5'-monophosphate dehydrogenase 2	Impdh2	IMDH2_MOUSE	56 179	7	173	50	107	7
Inosine triphosphate pyrophosphatase	Itpa	ITPA_MOUSE	22 225	5.5	84	72	128	15
Keratin, type I cytoskeletal 18	Krt18	K1C18_MOUSE	47 509	5.1	199	65	58	9
Keratin, type II cytoskeletal 7	Krt7	K2C7_MOUSE	50 678	5.6	137	52	55	4
Keratin, type II cytoskeletal 8	Krt8	K2C8_MOUSE	54 531	5.6	245	55	237	9
Cytosol aminopeptidase	Lap3	AMPL_MOUSE	56 505	8.7	126	47	58	5
L-lactate dehydrogenase B chain	Ldhb	LDHB_MOUSE	36 834	5.6	84	46	30	6
Galectin-1	Lgals1	LEG1_MOUSE	15 198	5.2	109	70	172	25
Galectin-2	Lgals2	LEG2_MOUSE	14 984	7.9	120	88	60	14
Lamin-B1	Lmnb1	LMNB1_MOUSE	66 973	5	265	60	134	5
α-2-macroglobulin receptor-associated protein	Lrpap1	AMRP_MOUSE	42 189	7.9	139	49	177	14
S-adenosylmethionine synthase isoform type-2	Mat2a	METK2_MOUSE	44 003	6	73	41	59	3
28S ribosomal protein S22, mitochondrial	Mrps22	RT22_MOUSE	41 281	9.2	112	45	97	9
Myosin-9	Myh9	MYH9_MOUSE	227 429	5.4	73	15	103	2
Nucleolin	Ncl	NUCL_MOUSE	76 734	4.5	113	26	179	7
Omega-amidase NIT2	Nit2	NIT2_MOUSE	30 825	6.5	112	59	75	9
Nucleoside diphosphate kinase A	Nme1	NDKA_MOUSE	17 311	7.7	125	72	223	30
Nucleoside diphosphate kinase B	Nme2	NDKB_MOUSE	17 466	7.8	160	84	287	30
Nucleophosmin	Npm1	NPM_MOUSE	32 711	4.5	53	33	136	10
Nuclear pore complex protein Nup54	Nup54	NUP54_MOUSE	55 812	6.6	55	21	23	3
Nuclear pore glycoprotein p62	Nup62	NUP62_MOUSE	53 336	5.1		13	43	5
Ornithine aminotransferase, mitochondrial	Oat	OAT_MOUSE	48 723	6.2	174	64	125	9
Poly(rC)-binding protein 1	Pcbp1	PCBP1_MOUSE	37 987	6.8	175	69	115	12
Protein disulfide-isomerase A3	Pdia3	PDIA3_MOUSE	57 099	5.8	254	55	90	5
Protein disulfide-isomerase A6	Pdia6	PDIA6_MOUSE	48 469	4.9	75	40	47	2
PDZ and LIM domain protein 1	Pdlim1	PDLI1_MOUSE	36 208	6.4	200	73	56	7
Phosphatidylethanolamine-binding protein 1	Pebp1	PEBP1_MOUSE	20 988	5.1	130	79	107	11
Phosphoglycerate mutase 1	Pgam1	PGAM1_MOUSE	28 928	6.8	157	66	192	21
Phosphoglycerate kinase 1	Pgk1	PGK1_MOUSE	44 921	9	136	52	128	7
6-phosphogluconolactonase	Pgls	6PGL_MOUSE	27 465	5.5	102	49	148	17
Pyruvate kinase isozymes M1/M2	Pkm2	KPYM_MOUSE	58 378	7.9	178	49	106	9
Purine nucleoside phosphorylase	Pnp	PNPH_MOUSE	32 541	5.8	119	67	138	13
Inorganic pyrophosphatase	Ppa1	IPYR_MOUSE	33 102	5.3	126	66	26	7
Peroxiredoxin-2	Prdx2	PRDX2_MOUSE	21 936	5.1	103	62	285	22
Peroxiredoxin-6	Prdx6	PRDX6_MOUSE	24 969	5.6	156	67	101	17
Proteasome subunit α type-1	Psma1	PSA1_MOUSE	29 813	6	71	52	140	17
Proteasome subunit α type-6	Psma6	PSA6_MOUSE	27 811	6.4	72	38	108	10
Proteasome subunit β type-3	Psmb3	PSB3_MOUSE	23 235	6.2	110	51	187	30
Proteasome subunit β type-4	Psmb4	PSB4_MOUSE	29 211	5.3	60	42	109	10
26S protease regulatory subunit 7	Psmc2	PRS7_MOUSE	49 016	5.6	166	60	72	8
26S protease regulatory subunit 6B	Psmc4	PRS6B_MOUSE	47 366	5	144	55	109	9
GTP-binding nuclear protein Ran	Ran	RAN_MOUSE	24 579	7.8	124	51	139	11
40S ribosomal protein S12	Rps12	RS12_MOUSE	14 858	7.7	77	62	95	11
RuvB-like 1	Ruvbl1	RUVB1_MOUSE	50 524	6	61	35	106	10
Protein S100-A11	S100a11	S10AB_MOUSE	11 247	5.1		36	147	27
Splicing factor, arginine/serine-rich 1	Sfrs1	SFRS1_MOUSE	27 842	10.8	80	43	156	18
Splicing factor, arginine/serine-rich 3	Sfrs3	SFRS3_MOUSE	19 546	12.3			87	14
Serine hydroxymethyltransferase, cytosolic	Shmt1	GLYC_MOUSE	53 065	6.5	98	43	19	2
Superoxide dismutase [Cu-Zn]	Sod1	SODC_MOUSE	16 104	6	83	45	126	31
Spermidine synthase	Srm	SPEE_MOUSE	34 543	5.2	141	73	129	15
Stress-induced-phosphoprotein 1	Stip1	STIP1_MOUSE	63 170	6.4	184	55	89	4
Stathmin	Stmn1	STMN1_MOUSE	17 264	5.7	28	24	69	8
Stomatin-like protein 2	Stoml2	STML2_MOUSE	38 475	9.5	144	61	165	15
TAR DNA-binding protein 43	Tardbp	TADBP_MOUSE	44 918	6.3	68	30	107	7
T-complex protein 1 subunit α	Tcp1	TCPA_MOUSE	60 867	5.8	61	27	28	4
Transcription intermediary factor 1-β	Trim28	TIF1B_MOUSE	90 558	5.4		10	139	4
Tubulin α-1B chain	Tuba1b	TBA1B_MOUSE	50 804	4.8	128	39	152	9
Tubulin α-1C chain	Tuba1c	TBA1C_MOUSE	50 562	4.8	53	24	52	6
Tubulin β-2A chain	Tubb2a	TBB2A_MOUSE	50 274	4.6	126	55	111	11
Tubulin β-2C chain	Tubb2c	TBB2C_MOUSE	50 255	4.6	150	56	49	8
Tubulin β-5 chain	Tubb5	TBB5_MOUSE	50 095	4.6	169	57	237	9
Thioredoxin	Txn	THIO_MOUSE	12 010	4.6	63	67	92	22
Thioredoxin-like protein 1	Txnl1	TXNL1_MOUSE	32 616	4.7	144	78	39	2
Ubiquitin-conjugating enzyme E2 N	Ube2n	UBE2N_MOUSE	17 184	6.2	119	71	20	6
Ubiquitin carboxyl-terminal hydrolase isozyme L1	Uchl1	UCHL1_MOUSE	25 165	5	77	64	16	8
Cytochrome b-c1 complex subunit 1, mitochondrial	Uqcrc1	QCR1_MOUSE	53 420	5.7	95	40	46	6
Transitional endoplasmic reticulum ATPase	Vcp	TERA_MOUSE	89 950	5	310	61	40	5
Voltage-dependent anion-selective channel protein 1	Vdac1	VDAC1_MOUSE	32 502	9.2	159	57	80	24
Vimentin	Vim	VIME_MOUSE	53 712	4.9	218	64	47	8

CPI: Calculated isoelectric point; PMF: Peptide mass fingerprint; MS/MS: Tandem mass spectrometry.

Table 2 Gene Ontology functional annotation of proteins which were regulated in this experiment according to their involvement in different biological processes

Biological process	Proteins	CPX > RA	CPX < RA	CPX > c	CPX < c	RA > c	RA < c
Monosaccharide metabolic/catabolic processes	5	Pgls	Eno1		Eno1		Eno1
		Gapdh			Pkm2		Ldhb
		Eno1					Pkm2
		Pkm2
Nucleobase, nucleoside, nucleotide, and nucleic acid biosynthetic processes	7	Atp5a1	Aprt	Atp5a1	Aprt	Nme2	Aprt
			Nme2		Atp5a1	Nme1	Atp5a1
			Nme1		Impdh2		Atp5h
					Nme2		Impdh2
					Nme1
					Pnp
RNA and mRNA processing	6	Sfrs1			Hnrnpk		Hnrnpc
					Tardbp		Sfrs3
					Pcbp1
Regulation of transcription	7	Ruvbl1		Nup62	Ube2n		Trim28
		Trim28			Tardbp		Ruvbl1
					Cbx3
					Hnrnpab
Embryonic development	5	Sfrs1	Psmc4	Atp5a1	Eno1	Myh9	Eno1
Embryonic development		Eno1	Eno1	Myh9	Atp5a1	Psmc4
Gene expression	16	Trim28	Rps12	Eif3f	Eef1a1		Sfrs3
		Sfrs1		Eif3i	Eif5a		Eif3i
		Ruvbl1			Eef1d		Hnrnpc
					Cbx3		Ruvbl1
					Hnrnpk		Eef1d
					Hnrnpab		Trim28
					Tardbp
					Pcbp1
Cell cycle processes	6	Ruvbl1		Myh9		Krt7	Npm1
						Myh9	Tubb5
							Stmn1
							Ruvbl1
Cell morphogenesis involved in differentiation	4	Trim28		Myh9	Uchl1	Myh9	Stmn1
Cell morphogenesis involved in differentiation					Hnrnpab		Trim28
Regulation of cell proliferation	4			Nup62	Nme2	Nme2	Npm1
Regulation of cell proliferation					Pnp
Regulation of signal transduction	4			Nup62	Ube2n		Npm1
Regulation of signal transduction							Hspa5

Ciclopirox olamine (CPX) > retinoic acid (RA): Proteins which were more than 2-fold higher expressed in CPX-treated cells compared to RA-treated cells; CPX < RA: Proteins which were more than 2-fold higher expressed in RA-treated cells compared to CPX-treated cells; CPX > c: Proteins which were more than 2-fold higher expressed in CPX-treated cells compared to control; CPX < c: Proteins which were more than 2-fold higher expressed in control compared to CPX-treated cells; RA > c: Proteins which were more than 2-fold higher expressed in RA-treated cells compared to control; RA < c: Proteins which were more than 2-fold higher expressed in control compared to RA-treated cells.

Table 3 Proteins which are upregulated upon ciclopirox olamine treatment compared to control

	k/CPX
	ESC	maGSC
Actb	0.13	0.19
Atp5a1¹	0.41	0.54
Ctsd	0.97	0.09
Eif3f¹	0.94	0.43
Eif3i¹	0.49	0.95
Etfa	0.63	0.39
Hspa9	0.92	0.31
Hspb1	0.63	0.05
Hspd1	0.19	0.21
Hspd1	0.36	0.69
Myh9¹	0.63	0.09
Nup62¹	0.30	0.60
S100a11		0.21
Tubb2a	1.00	0.21
Vdac1	0.58	0.18

¹The proteins are referred to in the text and following tables. CPX: Ciclopirox olamine; ESC: Embryonic stem cell; maGSC: Multipotent adult germline stem cell.

Table 4 Proteins which are downregulated upon ciclopirox olamine treatment compared to control

	k/CPX
	ESC	maGSC
Acp1	1.29	6.01
Acy1¹	1.38	2.81
Akr1b1	2.07	13.44
Aprt¹	4.80	3.60
Atp5a1¹	3.50	1.21
Capzb	3.04	2.35
Cbx3¹	1.72	2.12
Cct2¹	12.00	1.28
Cct5¹	1.06	2.02
Eef1a1¹	2.47	1.74
Eef1d¹	1.46	2.03
Eif5a¹	1.31	2.07
Eno1¹	3.56	1.60
Fscn1	3.31	1.49
Glod4	3.35	1.60
Gnb2l1	2.61	12.92
Hist1h2bb	2.31	2.10
Hist2h2ac	17.33	67.90
Hnrnpab¹	2.41	3.36
Hnrnpk¹	2.00	1.17
Hsp90aa1¹	1.19	6.79
Hsp90aa1¹	1.84	3.02
Hspa4¹	3.28	1.51
Hspa4	1.13	3.14
Hspa8	1.74	7.17
Hspd1	1.67	3.07
Impdh2¹	2.59	2.13
Impdh2¹	> 100	27.94
Krt18¹	2.31	1.44
Lgals2	2.82	8.45
Ncl¹	1.33	2.61
Nit2	1.24	2.13
Nme1¹	6.25	1.56
Nme2¹	4.77	4.51
Pcbp1¹	2.21	1.64
Pkm2¹	3.75	3.27
Pnp¹	1.20	2.62
Psmb4¹	1.01	2.32
Ruvbl1¹	1.02	2.14
Srm	1.64	3.63
Shmt1¹	> 100	> 100
Tardbp¹	1.38	3.52
Tcp1	1.47	3.76
Tuba1c¹	1.87	3.11
Tubb2c¹	1.38	3.41
Ube2n¹	1.31	6.45
Uchl1¹	2.66	1.66

¹The proteins are referred to in the text and following tables. CPX: Ciclopirox olamine; ESC: Embryonic stem cell; maGSC: Multipotent adult germline stem cell.

Table 5 Proteins which are downregulated upon retinoic acid treatment compared to control

Label	RA/k
	ESC	maGSC
Acp1	0.61	0.50
Actb¹	0.53	0.13
Acy1¹	0.13	0.70
Akr1b1	0.43	0.11
Aprt¹	0.46	0.39
Atp5a1¹	0.76	0.38
Atp5h¹	0.69	0.40
Cbx3	1.01	0.47
Cotl1¹	0.50	0.44
Eef1d¹	0.70	0.15
Eif3i¹	0.09	0.92
Eno1¹	0.24	0.04
Eno1¹	0.55	0.22
Fabp3		0.45
Fkbp4¹	0.90	0.40
Glo1¹	0.74	0.41
Glod4	0.82	0.30
Impdh2¹	0.76	0.35
Impdh2¹	0.54	0.20
Gnb2l1¹	0.66	0.15
Hnrnpc¹	0.76	0.43
Hsp90aa1	0.75	0.08
Hsp90aa1	0.49	0.06
Hsp90aa1	0.76	0.12
Hspa5¹	0.32	0.22
Hspa8¹	0.69	0.50
Hspb1¹	0.36	0.47
Hspb1¹	0.46	0.88
Hspb1¹	0.90	0.41
Hspd1¹	0.16	0.67
Hspd1¹	0.34	0.95
Itpa	0.57	0.07
Ldhb¹	0.42	0.43
Lgals2	0.29	0.03
Ncl¹	0.26	0.71
Npm1¹	0.46	0.04
Pebp1¹	0.89	0.42
Pkm2¹	0.38	0.15
Pkm2¹	0.32	0.65
Pkm2¹	0.42	0.76
Pkm2¹	0.21	0.43
Psmb4¹	0.62	0.43
Ruvbl1¹	0.63	0.22
Sfrs3¹	0.41	0.46
Shmt1¹	0.01	0.00
Srm	0.68	0.24
Trim28¹	0.23	0.11
Trim28¹	0.40	0.37
Tuba1c¹	0.27	0.71
Tubb5¹	0.70	0.25
Uqcrc1¹	0.24	0.22
Vdac1¹	0.30	0.52

¹The proteins are referred to in the text and following tables. RA: Retinoic acid; ESC: Embryonic stem cell; maGSC: Multipotent adult germline stem cell.

Table 6 Proteins which are upregulated upon retinoic acid treatment compared to control

	RA/k
	ESC	maGSC
Cct2	1.14	2.16
Hspa4	3.96	2.47
Krt7¹	1.01	38.11
Krt8	1.97	1.78
Myh9¹	3.06	3.24
Nme1¹	2.52	3.81
Nme2¹	1.20	2.48
Pdia6	1.72	20.48
Psmc4¹	2.17	2.17
Vcp	8.30	4.13
Vim¹	3.85	1.16

¹The proteins are referred to in the text and following tables. RA: Retinoic acid; ESC: Embryonic stem cell; maGSC: Multipotent adult germline stem cell.

Table 7 Gene Ontology functional annotation of proteins which were regulated in this experiment according to their involvement in different molecular function

Molecular function	Proteins	CPX > RA	CPX < RA	CPX > c	CPX < c	RA > c	RA < c
Nucleotide binding	41	Hsp90ab1	Atp5b	Tubb2a	Cct2	Cct2	Ldhb
		Fkbp4	Cct2	Etfa	Tardbp	Hspa4	Fkbp4
		Tubb5	Tardbp	Hspa9	Hspa4	Myh9	Tubb5
		Hspa5	Hspa4	Actb	Tuba1c	Nme2	Hnrnpc
		Tubb1b	Actb	Myh9	Hspa8	Vcp	Hspa5
		Gapdh	Hsp90aa1	Vdac1	Hnrnpab	Psmc4	Tuba1c
		Etfa	Ncl	Atp5a1	Eef1a1	Nme1	Hspa8
		Hspa9	Aprt	Hspd1	Tcp1		Actb
		Actb	Nme2		Hsp90aa1		Hsp90aa1
		Hsp90aa1	Vcp		Ncl		Ncl
		Sfrs1	Psmc4		Aprt		Sfrs3
		Vdac1	Nme1		Ube2n		Aprt
		Pkm2	Psmc2		Nme2		Vdac1
		Atp5a1			Cct5		Pkm2
		Ruvbl1			Nme1		Pebp1
		Hspd1			Pkm2		Atp5a1
					Atp5a1		Ruvbl1
					Ruvbl1		Hspd1
					Hspd1
GTP binding	8	Fkbp4	Nme1	Tubb2a	Eef1a1	Nme1	Fkbp4
		Tubb5			Nme1		Tubb5
		Tuba1b			Tuba1c		Tuba1c
ATPase activity	8	Atp5a1	Vcp	Atp5a1	Atp5a1	Vcp	Atp5a1
			Psmc4	Myh9	Hspa8	Psmc4	Atp5h
			Atp5b			Myh9	Hspa8
			Psmc2
Enzyme binding	8	Actb	Actb	Actb	Gnb2l1	Vim	Actb
		Npm1	Gnb2l1	Hspd1			Pebp1
		Hspd1		Hspa9			Hspd1
		Cotl1					Cotl1
		Hspa9
Cofactor binding	5	Gapdh		Etfa	Shmt1		Ldhb
		Etfa					Shmt1
Peptidase activity	6	Ctsd	Uchl1	Ctsd	Psmb4		Psmb4
		Eno1	Eno1		Acy1		Uqcrc1
					Uchl1		Acy1
					Eno1		Eno1
Metal ion binding	13	Trim28	Atp5b		Acy1	Pdia6	Acy1
		Sfrs1	Pdia6		Nme2	Nme2	Uqcrc1
		Pkm2	Nme2		Nme1	Nme1	Trim28 Pkm2
		Glo1	Nme1		Pkm2		Glo1
		Eno1	Eno1		Impdh2		Impdh2
					Eno1		Eno1

Ciclopirox olamine (CPX) > Retinoic acid (RA): Proteins which were more than 2-fold higher expressed in CPX-treated cells compared to RA-treated cells; CPX < RA: Proteins which were more than 2-fold higher expressed in RA-treated cells compared to CPX-treated cells; CPX > c: Proteins which were more than 2-fold higher expressed in CPX-treated cells compared to control; CPX < c: Proteins which were more than 2-fold higher expressed in control compared to CPX-treated cells; RA > c: Proteins which were more than 2-fold higher expressed in RA-treated cells compared to control; RA < c: Proteins which were more than 2-fold higher expressed in control compared to RA-treated cells.

Table 8 Proteins which are upregulated in stem cells upon ciclopirox olamine treatment compared to retinoic acid treatment

	RA/CPX
	ESC	maGSC
Actb*¹	0.12	0.10
Actb¹	0.14	0.15
Atp5a1¹	0.43	0.48
Cotl1	0.19	0.67
Ctsd	0.95	0.16
Eif3i	0.04	0.87
Eno1*¹	0.13	0.03
Eno1¹	0.57	0.40
Etfa	0.68	0.16
Fkbp4¹	0.46	0.43
Gapdh¹	0.35	0.59
Glo1	0.31	0.66
Glod4	0.85	0.36
Hsp90aa1	0.28	0.38
Hsp90aa1	0.43	0.13
Hsp90ab1	0.41	0.26
Hspa5*¹	0.17	0.13
Hspa9*¹	0.50	0.28
Hspb1*¹	0.29	0.04
Hspb1*¹	0.20	0.42
Hspb1¹	0.82	0.50
Hspd1¹	0.49	0.74
Hspd1¹	0.42	0.33
Itpa	0.21	0.08
Mat2a¹	0.41	0.14
Npm1¹	0.28	0.18
Nup62	0.57	0.26
Pgls¹	0.40	0.68
Pkm2¹	0.22	0.25
Pkm2¹	0.29	0.86
Prdx6	0.46	0.94
Ruvbl1¹	0.64	0.42
S100a11*¹	²	0.17
Sfrs1¹	0.70	0.30
Trim28¹	0.44	0.08
Trim28¹	0.42	0.44
Trim28¹	0.33	0.28
Tuba1b*¹	0.42	0.65
Tubb5¹	0.42	0.54
Tubb5¹	0.43	0.58
Vdac1*¹	0.17	0.09

¹The proteins are referred to in the text and following tables;

²The protein was not identified in embryonic stem cells. Proteins, which are assigned an asterisk, were upregulated upon ciclopirox olamine (CPX) treatment compared to control and concurrently downregulated upon retinoic acid (RA) treatment compared to control. ESC: Embryonic stem cell; maGSC: Multipotent adult germline stem cell.

Table 9 Proteins which are downregulated upon ciclopirox olamine treatment compared to retinoic acid treated stem cells

	RA/CPX
	ESC	maGSC
Actb¹	2.17	1.10
Aldh2	2.61	2.17
Aldh2	2.43	1.21
Aprt¹	2.20	1.42
Atp5b	1.15	2.17
Capzb	2.79	2.07
Cct2*¹	13.70	2.77
Eno1¹	2.48	2.02
Eno1¹	2.71	1.51
Fscn1	2.20	2.14
Gnb2l1	1.81	2.24
Hist1h2bb	7.53	1.62
Hist2h2ac	3.89	211.81
Hnrnpk	2.37	1.58
Hsp90aa1*¹	2.69	6.36
Hsp90aa1	6.36	4.33
Hspa4*¹	12.98	3.72
Hspa4	1.35	3.42
Krt7	> 100	1.14
Krt18*¹	4.04	1.76
Ncl	1.80	3.48
Nme1¹	2.63	1.57
Nme2*¹	5.72	11.15
Pdia6	1.74	6.33
Psmc2¹	2.87	1.20
Psmc4*¹	3.06	2.26
Rps12*¹	²	2.05
Tardbp	1.11	3.85
Uchl1¹	2.02	1.10
Vcp¹	8.94	2.57

¹The proteins are referred to in the text and following tables;

²The protein was not identified in embryonic stem cells. Proteins, which are assigned an asterisk, were downregulated upon ciclopirox olamine (CPX) treatment compared to control and concurrently upregulated upon retinoic acid (RA) treatment compared to control. ESC: Embryonic stem cell; maGSC: Multipotent adult germline stem cell.

Citation: Dihazi GH, Bibi A, Jahn O, Nolte J, Mueller GA, Engel W, Dihazi H. Impact of the antiproliferative agent ciclopirox olamine treatment on stem cells proteome. World J Stem Cells 2013; 5(1): 9-25
URL: https://www.wjgnet.com/1948-0210/full/v5/i1/9.htm
DOI: https://dx.doi.org/10.4252/wjsc.v5.i1.9