Zinc chloride exposure increases heme oxygenase-1 expression in MDPC-23 odontoblast-like cells

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• 作者：Hiroyo Karube ; Hisako Inamura ; Masato Matsuoka ; ^{matsuoka@research.twmu.ac.jp}
• 关键词：Akt ; amino kinase terminal ; DMSO ; dimethyl sulfoxide ; ERK ; extracellular signal-regulated protein kinase ; HO-1 ; heme oxygenase-1 ; JNK ; c-Jun NH2-terminal kinase ; MAPKs ; mitogen-activated protein kinases ; MK-2 ; MAPK-activated protein kinase-2 ; NF-¦ÊB ; nucl
• 刊名：Archives of Oral Biology
• 出版年：2013
• 出版时间：April, 2013
• 年：2013
• 卷：58
• 期：4
• 页码：355-361
• 全文大小：678 K

文摘

Objective

The aim of this study is to clarify the effects of zinc chloride (ZnCl₂) exposure on the induction of heme oxygenase-1 (HO-1) expression and its regulatory mechanisms in MDPC-23 mouse odontoblast-like cells.

Methods

MDPC-23 cells were incubated with ZnCl₂, and the levels of HO-1 protein, phosphorylated forms of mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated protein kinase (ERK), c-Jun NH₂-terminal kinase (JNK), and p38, and phosphorylated forms of amino kinase terminal (Akt) and nuclear factor-¦ÊB (NF-¦ÊB) p65 were determined with western immunoblotting. The level of HO-1 mRNA was determined with RT-PCR analysis. After pretreatment with inhibitors of ERK, JNK, p38, phosphoinositide-3 kinase (PI3K), and NF-¦ÊB, HO-1 protein level was determined in MDPC-23 cells exposed to ZnCl₂.

Results

Following exposure to 500 ¦ÌM ZnCl₂, the levels of both HO-1 mRNA and protein were markedly increased. The phosphorylated forms of ERK, JNK, and p38 increased after ZnCl₂ exposure. Furthermore, the expression of HO-1 was markedly suppressed by treatment with the p38 inhibitor, SB203580, and mildly suppressed by the MAPK/ERK kinase inhibitor, U0126. However, treatment with the JNK inhibitor, SP600125, did not suppress ZnCl₂-induced HO-1 expression. In addition, the phosphorylated forms of Akt, a downstream kinase of PI3K, and NF-¦ÊB p65 increased after ZnCl₂ exposure. Treatment with the PI3K inhibitor, LY294002, and the NF-¦ÊB inhibitor, Bay11-7082, suppressed ZnCl₂-induced HO-1 expression.

Conclusion

These results suggest that ZnCl₂ exposure induces HO-1 expression via multiple intracellular signalling pathways, including p38, ERK, PI3K/Akt, and NF-¦ÊB, in this odontoblast-like cell line.