Health & Environmental Research Online (HERO)


Print Feedback Export to File
1340672 
Journal Article 
Phosphorylation of histone H3 at serine 10 has an essential role in arsenite-induced expression of FOS, EGR1 and IL8 mRNA in cultured human cell lines 
Suzuki, T; Kita, K; Ochi, T 
2013 
Yes 
Journal of Applied Toxicology
ISSN: 0260-437X
EISSN: 1099-1263 
J Appl Toxicol. 
33 
746-755 
English 
Trivalent inorganic arsenite [iAs(III)] is known to alter the expression of a number of genes associated with transcription and cell proliferation, which was thought to be one of the possible mechanisms of arsenical carcinogenesis. However, the detailed mechanisms underlying iAs(III) induction of changes in gene expression are not fully understood. Here we examine the role of histone H3 phosphorylation at serine 10 (Ser(10) ) in gene regulation when the cells were treated with iAs(III). Among the 34 genes tested, iAs(III) induced mRNA expression of JUN, FOS, EGR1, HMOX1, HSPA1A, IL8, GADD45A, GADD45B and GADD153. Phosphorylation of histone H3 Ser(10) was induced by iAs(III) in interphase cells, and was effectively blocked by the ERKs pathway inhibitor (U0126). U0126 treatment significantly reduced constitutive mRNA expression of FOS and EGR1, and dramatically suppressed the induction of FOS, EGR1 and IL8 mRNA in iAs(III)-treated cells. The other genes, which were induced by iAs(III), were not affected by U0126 treatment. When the histone H3 nonphosphorylatable mutant of serine 10 (S10A) was overexpressed in cells, iAs(III) induction of FOS, EGR1and IL8 expression was significantly decreased as compared with wild-type cells. The other genes induced by iAs(III) were not changed in S10A cells nor by U0126 treatment. In addition, S10A cells were more resistant to iAs(III) cytotoxicity. These results indicated that the phosphorylation of histone H3 at Ser(10) through the ERKs pathway in interphase cells is an important regulatory event for iAs(III)-mediated gene expression. Aberrant gene expression seems to be an important cause of cytotoxicity and may have some relation to iAs(III) carcinogenicity. 
arsenite; histone H3; phosphorylation; epigenetics; gene expression 
IRIS
• Arsenic (Inorganic)
     1. Literature
          PubMed
          Lit search updates through Oct 2015
     3. Hazard ID Screening
          Other potentially supporting studies
     4. Adverse Outcome Pathways/Networks Screening
          Relevant
• Arsenic MOA
     4. Adverse Outcome Pathways
          Cell viability, cell proliferation, cell cycle changes (unrelated to regenerative proliferation)
          Epigenetic mechanisms
     5. Health Effect
          Cancer
     1. MOA Literature Screening
          Health Effect Screening
          MOA Cluster
• Inorganic Arsenic (7440-38-2) [Final 2025]
     1. Initial Lit Search
          PubMed
          ToxNet
          Considered New
          PubMed
          WOS
          ToxNet
          Excluded
               Toxnet Duplicates
          PubMed
          ToxNet
          Excluded
               Toxnet Duplicates
          ToxNet
          Excluded
               Toxnet Duplicates
          WOS
          ToxNet
          Excluded
               Toxnet Duplicates
          ToxNet
          Excluded
               Toxnet Duplicates
          ToxNet
          Excluded
               Toxnet Duplicates
     2. Lit Search Updates through Oct 2015
          PubMed
          WOS
          ToxNet
          Considered
     4. Considered through Oct 2015
     6. Cluster Filter through Oct 2015
     7. Other Studies through Oct 2015
          MOA
          iAs MOA Literature Categorization
               Endocrine Signaling
               Epigenetic Mechanisms
               Oxidative Stress