Nicotinamide N-Methyltransferase Suppression Participates in Nickel-Induced Histone H3 Lysine9 Dimethylation in BEAS-2B Cells.
Cell Physiol Biochem
; 41(5): 2016-2026, 2017.
Article
en En
| MEDLINE
| ID: mdl-28420001
ABSTRACT
BACKGROUND:
Nickel compounds are well-established human carcinogens with weak mutagenic activity. Histone methylation has been proposed to play an important role in nickel-induced carcinogenesis. Nicotinamide N-methyltransferase (NNMT) decreases histone methylation in several cancer cells by altering the cellular ratio of S-adenosylmethionine (SAM) to S-adenosylhomocysteine (SAH). However, the role of NNMT in nickel-induced histone methylation remains unclear.METHODS:
BEAS-2B cells were exposed to different concentrations of nickel chloride (NiCl2) for 72 h or 200 µM NiCl2 for different time periods. Histone H3 on lysine 9 (H3K9) mono-, di-, and trimethylation and NNMT protein levels were measured by western blot analysis. Expressions of NNMT mRNA and the H3k9me2-associated genes, mitogen-activated protein kinase 3 (MAP2K3) and dickkopf1 (DKK1), were determined by qPCR analysis. The cellular ratio of nicotinamide adenine dinucleotide (NAD+) to reduced NAD (NADH) and SAM/SAH ratio were determined.RESULTS:
Exposure of BEAS-2B cells to nickel increased H3K9 dimethylation (H3K9me2), suppressed the expressions of H3K9me2-associated genes (MAP2K3 and DKK1), and induced NNMT repression at both the protein and mRNA levels. Furthermore, over-expression of NNMT inhibited nickel-induced H3K9me2 and altered the cellular SAM/SAH ratio. Additionally, the NADH oxidant phenazine methosulfate (PMS) not only reversed the nickel-induced reduction in NAD+/NADH but also inhibited the increase in H3K9me2.CONCLUSIONS:
These findings indicate that the repression of NNMT may underlie nickel-induced H3K9 dimethylation by altering the cellular SAM/SAH ratio.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
S-Adenosilhomocisteína
/
S-Adenosilmetionina
/
Histonas
/
Nicotinamida N-Metiltransferasa
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Níquel
Límite:
Humans
Idioma:
En
Año:
2017
Tipo del documento:
Article