NDLI: 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.

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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.

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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.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Suzuki, Toshihide Kita, Kayoko Ochi, Takafumi
Description	Country affiliation: Japan Author Affiliation: Suzuki T ( Faculty of Pharmaceutical Sciences, Teikyo University, 1091-1 Sagamihara, Kanagawa, 252-5195, Japan. toshi-su@pharm.teikyo-u.ac.jp)
Abstract	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.
File Format	HTM / HTML
ISSN	0260437X
Issue Number	8
Volume Number	33
e-ISSN	10991263
Journal	Journal of Applied Toxicology
Language	English
Publisher	Wiley
Publisher Date	2013-08-01
Publisher Place	Great Britain (UK)
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Discipline Toxicology Arsenites Toxicity Early Growth Response Protein 1 Metabolism Histones Interleukin-8 Proto-oncogene Proteins C-fos Butadienes Pharmacology Genetics Enzyme Inhibitors Gene Expression Gene Expression Regulation Genetic Loci Hep G2 Cells Humans Nitriles Phosphorylation Rna, Messenger Serine Journal Article Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Toxicology

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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.

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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.