Protective Effects of Liposomal N-Acetylcysteine against Paraquat-Induced Cytotoxicity and Gene Expression

Table 1

Relative expression, via microarray analysis, of genes involved with cellular stress and toxicity in cells challenged with 0.25 mM PQ for 4 h following pretreatment with control, NAC-containing, or L-NAC-containing media. Genes are listed in order of decreasing fold change in cells pretreated with control media and challenged with PQ. Fold change is expressed relative to untreated control cells using the housekeeping genes B2M, HPRT1, RPL13A, and GAPDH. Note. the proposed housekeeping gene ACTB was significantly altered following PQ challenge, and was not used in this capacity in our study. 𝑛=3 independent experiments.

GeneBank accession no.	Gene name	Symbol	Fold change
			Control media + PQ	P value	NAC + PQ	P value	LNAC + PQ	P value
Oxidative/metabolic stress
NM_005953	Metallothionein 2A	MT2A	1.17	0.127	−1.07	0.616	1.33	0.229
NM_002133	Heme oxygenase (decycling) 1	HMOX1	1.14	0.531	1.34	0.170	−1.16	0.456
NM_000962	Prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase)	PTGS1	1.10	0.671	1.34	0.208	1.50	0.026**
NM_001885	Crystallin, alpha B	CRYAB	1.07	0.847	1.36	0.190	1.18	0.510
NM_002574	Peroxiredoxin 1	PRDX1	1.07	0.505	1.05	0.367	1.04	0.662
NM_000454	Superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD1	1.04	0.343	1.05	0.332	−1.07	0.200
NM_000581	Glutathione peroxidase 1	GPX1	1.01	0.812	1.05	0.395	−1.08	0.286
NM_000849	Glutathione S-transferase M3 (brain)	GSTM3	−1.02	0.833	−1.09	0.600	−1.03	0.743
NM_001752	Catalase	CAT	−1.03	0.740	−1.31	0.136	−1.16	0.168
NM_000637	Glutathione reductase	GSR	−1.08	0.594	−1.57	0.098	−1.46	0.111
NM_005809	Peroxiredoxin 2	PRDX2	−1.12	0.528	−1.01	0.892	−1.22	0.573
NM_001461	Flavin-containing monooxygenase 5	FMO5	−1.28	0.154	−1.53	0.072	−1.60	0.065
NM_000499	Cytochrome P450, family 1, subfamily A, polypeptide 1	CYP1A1	−1.40	0.057	1.09	0.583	4.44	0.003**
NM_000941	P450 (cytochrome) oxidoreductase	POR	−1.93	0.174	1.26	0.367	−2.70	0.122
NM_001979	Epoxide hydrolase 2, cytoplasmic	EPHX2	−2.06	0.066	−2.24	0.225	−1.22	0.369
NM_000773	Cytochrome P450, family 2, subfamily E, polypeptide 1	CYP2E1	—	—	—	—	—	—
NM_000780	Cytochrome P450, family 7, subfamily A, polypeptide 1	CYP7A1	—	—	—	—	—	—
NM_002021	Flavin-containing monooxygenase	FMO1	—	—	—	—	—	—
Heat shock
NM_005347	Heat shock 70 kDa protein 5 (glucose-regulated protein, 78 kDa)	HSPA5	1.35	0.004**	1.24	0.026**	−1.00	0.983
NM_007034	DnaJ (Hsp40) homolog, subfamily B, member 4	DNAJB4	1.32	0.052	1.10	0.568	−1.02	0.813
NM_001539	DnaJ (Hsp40) homolog, subfamily A, member 1	DNAJA1	1.29	0.048**	1.12	0.439	−1.08	0.443
NM_005526	Heat shock transcription factor 1	HSF1	1.14	0.074	1.08	0.253	1.13	0.354
NM_006644	Heat shock 105 kDa/110 kDa protein 1	HSPH1	1.14	0.253	1.03	0.551	1.03	0.612
NM_001; 040; 141	Heat shock protein 90 kDa alpha (cytosolic), class A member 2	HSP90AA2	1.08	0.200	1.05	0.557	1.09	0.279
NM_002157	Heat shock 10 kDa protein 1 (chaperonin 10)	HSPE1	1.07	0.414	−1.06	0.367	−1.07	0.503
NM_002156	Heat shock 60 kDa protein 1 (chaperonin)	HSPD1	1.06	0.671	−1.15	0.312	−1.08	0.406
NM_006597	Heat shock 70 kDa protein 8	HSPA8	1.02	0.922	−1.09	0.599	−1.33	0.060
NM_021979	Heat shock 70 kDa protein 2	HSPA2	1.01	0.908	−1.40	0.004**	−1.46	0.003**
NM_002154	Heat shock 70 kDa protein 4	HSPA4	−1.06	0.523	−1.47	0.036**	−1.71	0.004**
NM_007355	Heat shock protein 90 kDa alpha (cytosolic), class B member 1	HSP90AB1	−1.07	0.666	1.00	0.995	−1.61	0.058
NM_005345	Heat shock 70 kDa protein 1A	HSPA1A	−1.09	0.478	−1.29	0.102	1.00	0.957
NM_001540	Heat shock 27 kDa protein 1	HSPB1	−1.24	0.227	−1.00	0.924	−1.28	0.218
NM_005527	Heat shock 70 kDa protein 1-like	HSPA1L	−1.29	0.084	−1.65	0.032**	−1.42	0.077
NM_002155	Heat shock 70 kDa protein 6 (HSP70B′)	HSPA6	—	—	—	—	—	—
Proliferation/carcinogenesis
NM_001964	Early growth response 1	EGR1	1.97	0.039**	1.70	0.117	−1.24	0.395
NM_005190	Cyclin C	CCNC	1.30	0.226	1.02	0.995	1.18	0.561
NM_182649	Proliferating cell nuclear antigen	PCNA	1.14	0.283	−1.08	0.461	−1.04	0.678
NM_053056	Cyclin D1	CCND1	−1.03	0.885	−1.28	0.225	−1.02	0.803
NM_004060	Cyclin G1	CCNG1	−1.05	0.410	−1.02	0.316	1.07	0.435
NM_005225	E2F transcription factor 1	E2F1	−1.28	0.473	−1.16	0.450	−1.94	0.107
Growth arrest/senescence
NM_004864	Growth differentiation factor 15	GDF15	1.91	0.000**	1.96	0.003**	1.37	0.045**
NM_004083	DNA-damage-inducible transcript 3	DDIT3	1.87	0.000**	2.17	0.000**	1.46	0.020**
NM_000389	Cyclin-dependent kinase inhibitor 1A (p21, Cip1)	CDKN1A	1.50	0.002**	1.72	0.001**	1.88	0.000**
NM_001924	Growth arrest and DNA-damage-inducible, alpha	GADD45A	1.29	0.125	1.50	0.044**	−1.01	0.942
NM_002392	Mdm2, transformed 3T3 cell double minute 2, p53-binding protein (mouse)	MDM2	1.26	0.119	−1.01	0.999	1.25	0.112
NM_000546	Tumor protein p53	TP53	1.14	0.294	−1.10	0.546	−1.11	0.353
NM_002178	Insulin-like growth factor-binding protein 6	IGFBP6	−1.19	0.186	1.04	0.761	−1.58	0.032**
Inflammatory
NM_001562	Interleukin 18 (interferon-gamma-inducing factor)	IL18	1.49	0.010**	1.26	0.106	1.28	0.016**
NM_000575	Interleukin 1, alpha	IL1A	1.47	0.085	1.18	0.481	1.88	0.020**
NM_000602	Serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1	SERPINE1	1.38	0.035**	1.34	0.096	1.01	0.976
NM_000595	Lymphotoxin alpha (TNF superfamily, member 1)	LTA	1.22	0.458	1.38	0.141	−2.19	0.060
NM_003998	Nuclear factor of kappa light polypeptide gene enhancer in B cells 1 (p105)	NFKB1	1.22	0.004**	1.12	0.092	1.36	0.000**
NM_002415	Macrophage migration inhibitory factor (glycosylation-inhibiting factor)	MIF	1.02	0.505	1.13	0.043**	−1.06	0.331
NM_000576	Interleukin 1, beta	IL1B	−1.02	0.948	−1.69	0.357	−1.02	0.936
NM_002989	Chemokine (C-C motif) ligand 21	CCL21	—	—	—	—	—	—
NM_002983	Chemokine (C-C motif) ligand 3	CCL3	—	—	—	—	—	—
NM_002984	Chemokine (C-C motif) ligand 4	CCL4	—	—	—	—	—	—
NM_001565	Chemokine (C-X-C motif) ligand 10	CXCL10	—	—	—	—	—	—
DNA damage/repair
NM_000051	Ataxia telangiectasia mutated	ATM	1.21	0.318	−1.38	0.197	−1.07	0.727
NM_005431	X-ray repair complementing defective repair in Chinese hamster cells 2	XRCC2	1.19	0.125	−1.26	0.261	1.10	0.303
NM_003362	Uracil-DNA glycosylase	UNG	1.11	0.315	−1.01	0.882	−1.01	0.890
NM_000122	Excision repair cross-complementing rodent repair deficiency, complementation group 3 (xeroderma pigmentosum group B complementing)	ERCC3	1.07	0.612	−1.26	0.271	−1.20	0.229
NM_005053	RAD23 homolog A (S. cerevisiae)	RAD23A	1.04	0.764	−1.00	0.956	−1.23	0.265
NM_007194	CHK2 checkpoint homolog (S. pombe)	CHEK2	1.03	0.844	−1.32	0.111	−1.23	0.100
NM_001923	Damage-specific DNA-binding protein 1, 127 kDa	DDB1	−1.11	0.403	−1.26	0.241	−1.54	0.041**
NM_001983	Excision repair cross-complementing rodent repair deficiency, complementation group 1 (includes overlapping antisense sequence)	ERCC1	−1.16	0.463	1.08	0.666	−1.48	0.278
NM_006297	X-ray repair complementing defective repair in Chinese hamster cells 1	XRCC1	−1.25	0.235	−1.29	0.226	−1.64	0.071
NM_007120	UDP glucuronosyltransferase 1 family, polypeptide A4	UGT1A4	−1.30	0.319	−2.04	0.071	−1.50	0.283
Apoptosis signalling
NM_001230	Caspase 10, apoptosis-related cysteine peptidase	CASP10	1.71	0.006**	1.25	0.194	1.35	0.110
NM_001154	Annexin A5	ANXA5	1.42	0.025**	1.17	0.073	1.42	0.004**
NM_020529	Nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha	NFKBIA	1.20	0.097	1.35	0.014**	1.47	0.017**
NM_001228	Caspase 8, apoptosis-related cysteine peptidase	CASP8	1.15	0.184	−1.08	0.571	1.36	0.017**
NM_004324	BCL2-associated X protein	BAX	−1.04	0.656	−1.12	0.503	−1.30	0.069
NM_003810	Tumor necrosis factor (ligand) superfamily, member 10	TNFSF10	−1.09	0.788	−1.15	0.444	−1.53	0.110
NM_033292	Caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta, convertase)	CASP1	−1.11	0.818	−1.24	0.150	−1.19	0.627
NM_001065	Tumor necrosis factor receptor superfamily, member 1A	TNFRSF1A	−1.29	0.235	−1.15	0.610	−1.64	0.081
NM_138578	BCL2-like 1	BCL2L1	−1.46	0.028**	−1.37	0.257	−1.42	0.340
Housekeeping
NM_001101	Actin, beta	ACTB	1.35	0.018**	−1.17	0.251	1.23	0.152
NM_004048	Beta-2-microglobulin	B2M	—	—	—	—	—	—
NM_000194	Hypoxanthine phosphoribosyltransferase 1 (Lesch-Nyhan syndrome)	HPRT1	—	—	—	—	—	—
NM_012423	Ribosomal protein L13a	RPL13A	—	—	—	—	—	—
NM_002046	Glyceraldehyde-3-phosphate dehydrogenase	GAPDH	—	—	—	—	—	—

^∗∗𝑃<.05.