Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTE2KVZV)

• DOT Name: Amiloride-sensitive sodium channel subunit alpha (SCNN1A)
• Synonyms: Alpha-NaCH; Epithelial Na(+) channel subunit alpha; Alpha-ENaC; ENaCA; Nonvoltage-gated sodium channel 1 subunit alpha; SCNEA
• Gene Name: SCNN1A
• Related Disease:
  Autosomal recessive pseudohypoaldosteronism type 1
  Familial hypercholesterolemia
  Hypercholesterolemia, familial, 1
  Adult glioblastoma
  Autosomal dominant pseudohypoaldosteronism type 1
  Bronchiectasis with or without elevated sweat chloride 2
  Embryonal neoplasm
  Germ cell tumor
  Glioblastoma multiforme
  Hyperinsulinemia
  Idiopathic bronchiectasis
  Lung cancer
  Lung carcinoma
  Nephrotic syndrome
  Polycystic ovarian syndrome
  Pre-eclampsia
  Pseudohypoaldosteronism type 2
  Small-cell lung cancer
  Nephropathy
  Brugada syndrome
  Liddle syndrome
  Amyotrophic lateral sclerosis
  Ankylosing spondylitis
  Breast cancer
  Breast carcinoma
  Congenital alveolar dysplasia
  Essential hypertension
  High blood pressure
  Liddle syndrome 3
  Nervous system inflammation
  Neuroblastoma
  Pelger-Huet anomaly
  Pulmonary disease
  Pulmonary edema
• UniProt ID: SCNNA_HUMAN
• PDB ID: 2M3O; 6BQN; 6WTH
• Pfam ID: PF00858
• Sequence:
  MEGNKLEEQDSSPPQSTPGLMKGNKREEQGLGPEPAAPQQPTAEEEALIEFHRSYRELFE
  FFCNNTTIHGAIRLVCSQHNRMKTAFWAVLWLCTFGMMYWQFGLLFGEYFSYPVSLNINL
  NSDKLVFPAVTICTLNPYRYPEIKEELEELDRITEQTLFDLYKYSSFTTLVAGSRSRRDL
  RGTLPHPLQRLRVPPPPHGARRARSVASSLRDNNPQVDWKDWKIGFQLCNQNKSDCFYQT
  YSSGVDAVREWYRFHYINILSRLPETLPSLEEDTLGNFIFACRFNQVSCNQANYSHFHHP
  MYGNCYTFNDKNNSNLWMSSMPGINNGLSLMLRAEQNDFIPLLSTVTGARVMVHGQDEPA
  FMDDGGFNLRPGVETSISMRKETLDRLGGDYGDCTKNGSDVPVENLYPSKYTQQVCIHSC
  FQESMIKECGCAYIFYPRPQNVEYCDYRKHSSWGYCYYKLQVDFSSDHLGCFTKCRKPCS
  VTSYQLSAGYSRWPSVTSQEWVFQMLSRQNNYTVNNKRNGVAKVNIFFKELNYKTNSESP
  SVTMVTLLSNLGSQWSLWFGSSVLSVVEMAELVFDLLVIMFLMLLRRFRSRYWSPGRGGR
  GAQEVASTLASSPPSHFCPHPMSLSLSQPGPAPSPALTAPPPAYATLGPRPSPGGSAGAS
  SSTCPLGGP
• Function: Sodium permeable non-voltage-sensitive ion channel inhibited by the diuretic amiloride. Mediates the electrodiffusion of the luminal sodium (and water, which follows osmotically) through the apical membrane of epithelial cells. Plays an essential role in electrolyte and blood pressure homeostasis, but also in airway surface liquid homeostasis, which is important for proper clearance of mucus. Controls the reabsorption of sodium in kidney, colon, lung and eccrine sweat glands. Also plays a role in taste perception.
• Tissue Specificity: Expressed in the female reproductive tract, from the fimbrial end of the fallopian tube to the endometrium (at protein level) . Expressed in kidney (at protein level). In the respiratory tract, expressed in the bronchial epithelium (at protein level). Highly expressed in lung. Detected at intermediate levels in pancreas and liver, and at low levels in heart and placenta . in skin, expressed in keratinocytes, melanocytes and Merkel cells of the epidermal sub-layers, stratum basale, stratum spinosum and stratum granulosum (at protein level) . Expressed in the outer root sheath of the hair follicles (at protein level) . Detected in both peripheral and central cells of the sebaceous gland (at protein level) . Expressed by eccrine sweat glands (at protein level) . In skin, also expressed by arrector pili muscle cells and intradermal adipocytes . Isoform 1 and isoform 2 predominate in all tissues. Expression of isoform 3, isoform 4 and isoform 5 is very low or not detectable, except in lung and heart .
• KEGG Pathway:
  Taste transduction (hsa04742)
  Aldosterone-regulated sodium reabsorption (hsa04960)
• Reactome Pathway:
  Sensory perception of salty taste (R-HSA-9730628)
  Stimuli-sensing channels (R-HSA-2672351)

Molecular Interaction Atlas (MIA) of This DOT

34 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autosomal recessive pseudohypoaldosteronism type 1	DIS7WSWQ	Definitive	Autosomal recessive	[1]
Familial hypercholesterolemia	DISC06IX	Definitive	Genetic Variation	[2]
Hypercholesterolemia, familial, 1	DISU411W	Definitive	Genetic Variation	[2]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[3]
Autosomal dominant pseudohypoaldosteronism type 1	DIS4FXQ4	Strong	Biomarker	[4]
Bronchiectasis with or without elevated sweat chloride 2	DISFFTJU	Strong	Autosomal dominant	[5]
Embryonal neoplasm	DIS5MQSB	Strong	Biomarker	[6]
Germ cell tumor	DIS62070	Strong	Biomarker	[6]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[3]
Hyperinsulinemia	DISIDWT6	Strong	Altered Expression	[7]
Idiopathic bronchiectasis	DISZ7YNI	Strong	GermlineCausalMutation	[8]
Lung cancer	DISCM4YA	Strong	Altered Expression	[9]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[9]
Nephrotic syndrome	DISSPSC2	Strong	Biomarker	[10]
Polycystic ovarian syndrome	DISZ2BNG	Strong	Biomarker	[11]
Pre-eclampsia	DISY7Q29	Strong	Biomarker	[12]
Pseudohypoaldosteronism type 2	DISFTCHO	Strong	Biomarker	[4]
Small-cell lung cancer	DISK3LZD	Strong	Altered Expression	[9]
Nephropathy	DISXWP4P	moderate	Biomarker	[13]
Brugada syndrome	DISSGN0E	Supportive	Autosomal dominant	[14]
Liddle syndrome	DISY0X0N	Supportive	Autosomal dominant	[15]
Amyotrophic lateral sclerosis	DISF7HVM	Limited	Genetic Variation	[16]
Ankylosing spondylitis	DISRC6IR	Limited	Genetic Variation	[17]
Breast cancer	DIS7DPX1	Limited	Biomarker	[18]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[18]
Congenital alveolar dysplasia	DIS1IYUN	Limited	Genetic Variation	[19]
Essential hypertension	DIS7WI98	Limited	Genetic Variation	[20]
High blood pressure	DISY2OHH	Limited	Genetic Variation	[21]
Liddle syndrome 3	DIS8RBWY	Limited	Autosomal dominant	[1]
Nervous system inflammation	DISB3X5A	Limited	Biomarker	[22]
Neuroblastoma	DISVZBI4	Limited	Biomarker	[23]
Pelger-Huet anomaly	DISCW4OI	Limited	Genetic Variation	[24]
Pulmonary disease	DIS6060I	Limited	Biomarker	[25]
Pulmonary edema	DISNPHO6	Limited	Biomarker	[26]

3 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Amiloride-sensitive sodium channel subunit alpha (SCNN1A).	[27]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Amiloride-sensitive sodium channel subunit alpha (SCNN1A).	[34]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Amiloride-sensitive sodium channel subunit alpha (SCNN1A).	[48]

28 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin affects the expression of Amiloride-sensitive sodium channel subunit alpha (SCNN1A).	[28]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Amiloride-sensitive sodium channel subunit alpha (SCNN1A).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Amiloride-sensitive sodium channel subunit alpha (SCNN1A).	[30]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Amiloride-sensitive sodium channel subunit alpha (SCNN1A).	[31]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Amiloride-sensitive sodium channel subunit alpha (SCNN1A).	[32]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Amiloride-sensitive sodium channel subunit alpha (SCNN1A).	[33]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Amiloride-sensitive sodium channel subunit alpha (SCNN1A).	[35]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Amiloride-sensitive sodium channel subunit alpha (SCNN1A).	[36]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Amiloride-sensitive sodium channel subunit alpha (SCNN1A).	[37]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Amiloride-sensitive sodium channel subunit alpha (SCNN1A).	[38]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Amiloride-sensitive sodium channel subunit alpha (SCNN1A).	[39]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Amiloride-sensitive sodium channel subunit alpha (SCNN1A).	[40]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Amiloride-sensitive sodium channel subunit alpha (SCNN1A).	[41]
Isotretinoin	DM4QTBN	Approved	Isotretinoin increases the expression of Amiloride-sensitive sodium channel subunit alpha (SCNN1A).	[42]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Amiloride-sensitive sodium channel subunit alpha (SCNN1A).	[43]
Amphotericin B	DMTAJQE	Approved	Amphotericin B decreases the expression of Amiloride-sensitive sodium channel subunit alpha (SCNN1A).	[44]
Hydrocortisone	DMGEMB7	Approved	Hydrocortisone increases the expression of Amiloride-sensitive sodium channel subunit alpha (SCNN1A).	[45]
Aldosterone	DM9S2JW	Approved	Aldosterone increases the expression of Amiloride-sensitive sodium channel subunit alpha (SCNN1A).	[46]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Amiloride-sensitive sodium channel subunit alpha (SCNN1A).	[41]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Amiloride-sensitive sodium channel subunit alpha (SCNN1A).	[41]
APR-246	DMNFADH	Phase 2	APR-246 increases the expression of Amiloride-sensitive sodium channel subunit alpha (SCNN1A).	[47]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Amiloride-sensitive sodium channel subunit alpha (SCNN1A).	[49]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Amiloride-sensitive sodium channel subunit alpha (SCNN1A).	[50]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Amiloride-sensitive sodium channel subunit alpha (SCNN1A).	[51]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Amiloride-sensitive sodium channel subunit alpha (SCNN1A).	[52]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Amiloride-sensitive sodium channel subunit alpha (SCNN1A).	[53]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Amiloride-sensitive sodium channel subunit alpha (SCNN1A).	[54]
Lithium chloride	DMHYLQ2	Investigative	Lithium chloride increases the expression of Amiloride-sensitive sodium channel subunit alpha (SCNN1A).	[55]

References

• [1] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [2] Different genes and polymorphisms affecting high-density lipoprotein cholesterol levels in Greek familial hypercholesterolemia patients.Genet Test. 2006 Fall;10(3):192-9. doi: 10.1089/gte.2006.10.192.
• [3] Interaction of ASIC1 and ENaC subunits in human glioma cells and rat astrocytes.Am J Physiol Cell Physiol. 2011 Jun;300(6):C1246-59. doi: 10.1152/ajpcell.00199.2010. Epub 2011 Feb 23.
• [4] Association of a sodium channel alpha subunit promoter variant with blood pressure.J Am Soc Nephrol. 2002 Jan;13(1):80-85. doi: 10.1681/ASN.V13180.
• [5] Epithelial sodium channels (ENaC) are uniformly distributed on motile cilia in the oviduct and the respiratory airways. Histochem Cell Biol. 2012 Mar;137(3):339-53. doi: 10.1007/s00418-011-0904-1. Epub 2011 Dec 30.
• [6] Retinoic acid represses a cassette of candidate pluripotency chromosome 12p genes during induced loss of human embryonal carcinoma tumorigenicity. Biochim Biophys Acta. 2005 Oct 15;1731(1):48-56. doi: 10.1016/j.bbaexp.2005.08.006. Epub 2005 Sep 1.
• [7] Insulin ameliorates pulmonary edema through the upregulation of epithelial sodium channel via the PI3K/SGK1 pathway in mice with lipopolysaccharideinduced lung injury.Mol Med Rep. 2019 Mar;19(3):1665-1677. doi: 10.3892/mmr.2019.9809. Epub 2019 Jan 2.
• [8] Mutations in the amiloride-sensitive epithelial sodium channel in patients with cystic fibrosis-like disease.Hum Mutat. 2009 Jul;30(7):1093-103. doi: 10.1002/humu.21011.
• [9] The Epithelial Sodium Channel (ENaC) Is a Downstream Therapeutic Target of ASCL1 in Pulmonary Neuroendocrine Tumors.Transl Oncol. 2018 Apr;11(2):292-299. doi: 10.1016/j.tranon.2018.01.004. Epub 2018 Feb 2.
• [10] Increased expression and apical targeting of renal ENaC subunits in puromycin aminonucleoside-induced nephrotic syndrome in rats.Am J Physiol Renal Physiol. 2004 May;286(5):F922-35. doi: 10.1152/ajprenal.00277.2003. Epub 2004 Jan 6.
• [11] Progesterone resistance in PCOS endometrium: a microarray analysis in clomiphene citrate-treated and artificial menstrual cycles.J Clin Endocrinol Metab. 2011 Jun;96(6):1737-46. doi: 10.1210/jc.2010-2600. Epub 2011 Mar 16.
• [12] [Characterization of the epithelial sodium channel in human pre-eclampsia syncytiotrophoblast].Medicina (B Aires). 2006;66(1):31-5.
• [13] Mutations in the beta-subunit of the epithelial Na+ channel in patients with a cystic fibrosis-like syndrome.Hum Mol Genet. 2005 Nov 15;14(22):3493-8. doi: 10.1093/hmg/ddi374. Epub 2005 Oct 5.
• [14] Genetic interpretation and clinical translation of minor genes related to Brugada syndrome. Hum Mutat. 2019 Jun;40(6):749-764. doi: 10.1002/humu.23730. Epub 2019 Mar 29.
• [15] A Missense Mutation in the Extracellular Domain of ENaC Causes Liddle Syndrome. J Am Soc Nephrol. 2017 Nov;28(11):3291-3299. doi: 10.1681/ASN.2016111163. Epub 2017 Jul 14.
• [16] Association analysis of four candidate genetic variants with sporadic amyotrophic lateral sclerosis in a Chinese population.Neurol Sci. 2014 Jul;35(7):1089-95. doi: 10.1007/s10072-014-1656-1. Epub 2014 Feb 4.
• [17] Evidence of genetic association between TNFRSF1A encoding the p55 tumour necrosis factor receptor, and ankylosing spondylitis in UK Caucasians.Clin Exp Rheumatol. 2012 Jan-Feb;30(1):110-3. Epub 2012 Mar 7.
• [18] Recurrent read-through fusion transcripts in breast cancer.Breast Cancer Res Treat. 2014 Jul;146(2):287-97. doi: 10.1007/s10549-014-3019-2. Epub 2014 Jun 15.
• [19] Association of SCNN1A Single Nucleotide Polymorphisms with neonatal respiratory distress syndrome.Sci Rep. 2015 Nov 27;5:17317. doi: 10.1038/srep17317.
• [20] Lack of association of functional variants in alpha-ENaC gene and essential hypertension in two ethnic groups in China.Kidney Blood Press Res. 2008;31(4):268-73. doi: 10.1159/000151286. Epub 2008 Aug 15.
• [21] Enhanced expression of the Epithelial Sodium Channel in neutrophils from hypertensive patients.Biochim Biophys Acta Biomembr. 2019 Feb 1;1861(2):387-402. doi: 10.1016/j.bbamem.2018.11.003. Epub 2018 Nov 10.
• [22] Progression of experimental autoimmune encephalomyelitis is associated with up-regulation of major sodium transporters in the mouse kidney cortex under a normal salt diet.Cell Immunol. 2017 Jul;317:18-25. doi: 10.1016/j.cellimm.2017.04.006. Epub 2017 Apr 18.
• [23] Identification of epigenetically regulated genes that predict patient outcome in neuroblastoma.BMC Cancer. 2011 Feb 11;11:66. doi: 10.1186/1471-2407-11-66.
• [24] Expression of the epithelial sodium channel (ENaC) in the endometrium - Implications for fertility in a patient with pseudohypoaldosteronism.J Steroid Biochem Mol Biol. 2018 Oct;183:137-141. doi: 10.1016/j.jsbmb.2018.06.007. Epub 2018 Jun 6.
• [25] Inhaled ENaC antisense oligonucleotide ameliorates cystic fibrosis-like lung disease in mice.J Cyst Fibros. 2017 Nov;16(6):671-680. doi: 10.1016/j.jcf.2017.05.003. Epub 2017 May 20.
• [26] Defective respiratory amiloride-sensitive sodium transport predisposes to pulmonary oedema and delays its resolution in mice.J Physiol. 2004 Nov 1;560(Pt 3):857-65. doi: 10.1113/jphysiol.2004.066704. Epub 2004 Aug 12.
• [27] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [28] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [29] Retinoic acid represses a cassette of candidate pluripotency chromosome 12p genes during induced loss of human embryonal carcinoma tumorigenicity. Biochim Biophys Acta. 2005 Oct 15;1731(1):48-56. doi: 10.1016/j.bbaexp.2005.08.006. Epub 2005 Sep 1.
• [30] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [31] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [32] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [33] Long-term estrogen exposure promotes carcinogen bioactivation, induces persistent changes in gene expression, and enhances the tumorigenicity of MCF-7 human breast cancer cells. Toxicol Appl Pharmacol. 2009 Nov 1;240(3):355-66.
• [34] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [35] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [36] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [37] Androgen receptor-mediated regulation of the alpha-subunit of the epithelial sodium channel in human kidney. Hypertension. 2005 Oct;46(4):787-98. doi: 10.1161/01.HYP.0000184362.61744.c1. Epub 2005 Sep 19.
• [38] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [39] Endometrial receptivity is affected in women with high circulating progesterone levels at the end of the follicular phase: a functional genomics analysis. Hum Reprod. 2011 Jul;26(7):1813-25.
• [40] Dissecting progressive stages of 5-fluorouracil resistance in vitro using RNA expression profiling. Int J Cancer. 2004 Nov 1;112(2):200-12. doi: 10.1002/ijc.20401.
• [41] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [42] Gene microarray analysis of human renal cell carcinoma: the effects of HDAC inhibition and retinoid treatment. Cancer Biol Ther. 2008 Oct;7(10):1607-18.
• [43] Chronic ethanol exposure increases goosecoid (GSC) expression in human embryonic carcinoma cell differentiation. J Appl Toxicol. 2014 Jan;34(1):66-75.
• [44] Differential expression of microRNAs and their predicted targets in renal cells exposed to amphotericin B and its complex with copper (II) ions. Toxicol Mech Methods. 2017 Sep;27(7):537-543. doi: 10.1080/15376516.2017.1333554. Epub 2017 Jun 8.
• [45] P2Y receptor regulation of sodium transport in human mammary epithelial cells. Am J Physiol Cell Physiol. 2007 Nov;293(5):C1472-80. doi: 10.1152/ajpcell.00068.2007. Epub 2007 Aug 22.
• [46] Epithelial sodium channel in a human trophoblast cell line (BeWo). J Membr Biol. 2008 Jun;223(3):127-39. doi: 10.1007/s00232-008-9119-3. Epub 2008 Jul 30.
• [47] Mutant p53 reactivation by PRIMA-1MET induces multiple signaling pathways converging on apoptosis. Oncogene. 2010 Mar 4;29(9):1329-38. doi: 10.1038/onc.2009.425. Epub 2009 Nov 30.
• [48] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [49] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [50] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [51] Environmentally relevant levels of bisphenol A affect uterine decidualization and embryo implantation through the estrogen receptor/serum and glucocorticoid-regulated kinase 1/epithelial sodium ion channel -subunit pathway in a mouse model. Fertil Steril. 2018 Apr;109(4):735-744.e1. doi: 10.1016/j.fertnstert.2017.12.003. Epub 2018 Mar 28.
• [52] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [53] Regulation of chromatin assembly and cell transformation by formaldehyde exposure in human cells. Environ Health Perspect. 2017 Sep 21;125(9):097019.
• [54] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [55] Effects of lithium and valproic acid on gene expression and phenotypic markers in an NT2 neurosphere model of neural development. PLoS One. 2013;8(3):e58822.