Cyclooxygenase-2 induction by arsenite through the IKKbeta/NFkappaB pathway exerts an antiapoptotic effect in mouse epidermal Cl41 cells.

Cyclooxygenase-2 induction by arsenite through the IKKbeta/NFkappaB pathway exerts an antiapoptotic effect in mouse epidermal Cl41 cells. Research Abstract Details 

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Cyclooxygenase-2 induction by arsenite through the IKKbeta/NFkappaB pathway exerts an antiapoptotic effect in mouse epidermal Cl41 cells. Abstract Text:

Weiming Ouyang,Dongyun Zhang,Qian Ma,Jingxia Li,Chuanshu Huang,

BACKGROUND: Arsenic contamination has become a major public health concern worldwide. Epidemiologic data show that long-term arsenic exposure results in the risk of skin cancer. However, the mechanisms underlying carcinogenic effects of arsenite on skin remain to be studied. OBJECTIVES: In the present study we evaluated cyclooxygenase-2 (COX-2) expression, the signaling pathways leading to COX-2 induction, and its antiapoptotic function in the response to arsenite exposure in mouse epidermal JB6 Cl41 cells. METHODS: We used the luciferase reporter assay and Western blots to determine COX-2 induction by arsenite. We utilized dominant negative mutant, genetic knockout, gene knockdown, and gene overexpression approaches to elucidate the signaling pathway involved in COX-2 induction and its protective effect on cell apoptosis. RESULTS: The induction of COX-2 by arsenite was inhibited in Cl41 cells transfected with IKKbeta-KM, a dominant mutant inhibitor of kbeta (Ikbeta) kinase (IKKbeta), and in IKKbeta-knockout (IKKbeta(-/-)) mouse embryonic fibroblasts (MEFs). IKKbeta/nuclear factor kappaB (NFkappaB) pathway-mediated COX-2 induction exerted an antiapoptotic effect on the cells exposed to arsenite because cell apoptosis was significantly enhanced in the Cl41 cells transfected with IKKbeta-KM or COX-2 small interference RNA (siCOX-2). In addition, IKKbeta(-/-) MEFs stably transfected with COX-2 showed more resistance to arsenite-induced apoptosis compared with the same control vector-transfected cells. CONCLUSIONS: These results demonstrate that arsenite exposure can induce COX-2 expression through the IKKbeta/NFkappaB pathway, which thereby exerts an antiapoptotic effect in response to arsenite. In light of the importance of apoptosis evasion during carcinogenesis, we anticipate that COX-2 induction may be at least partially responsible for the carcinogenic effect of arsenite on skin.

Cyclooxygenase-2 induction by arsenite through the IKKbeta/NFkappaB pathway exerts an antiapoptotic effect in mouse epidermal Cl41 cells. Publishing Authors By Initials

W Ouyang,D Zhang,Q Ma,J Li,C Huang,

For similar neoplasms: neoplasms by site: skin neoplasms research abstracts see: neoplasms: neoplasms by site: skin neoplasms research

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Cyclooxygenase-2 induction by arsenite through the IKKbeta/NFkappaB pathway exerts an antiapoptotic effect in mouse epidermal Cl41 cells. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Environmental health perspectives

VOLUME: 115

Page Numbers: 513-8

Journal Abbreviation:

ISSN: 0091-6765

DAY: 14

MONTH: 12

YEAR: 2006

Cyclooxygenase-2 induction by arsenite through the IKKbeta/NFkappaB pathway exerts an antiapoptotic effect in mouse epidermal Cl41 cells. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 330411

Cyclooxygenase-2 induction by arsenite through the IKKbeta/NFkappaB pathway exerts an antiapoptotic effect in mouse epidermal Cl41 cells. Keywords Mesh Terms:

KEYWORDS: Skin Neoplasms

MESH TERMS: chemically induced

Chemical & Substance for Abstract: Cyclooxygenase-2 induction by arsenite through the IKKbeta/NFkappaB pathway exerts an antiapoptotic effect in mouse epidermal Cl41 cells. Information

Substance Name: Ikbkb protein, mouse

Registry Number: EC 2.7.1.37

Grant and Affiliation Information for Cyclooxygenase-2 induction by arsenite through the IKKbeta/NFkappaB pathway exerts an antiapoptotic effect in mouse epidermal Cl41 cells.

AFFILIATION: Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo, New York, USA.

Country: United States

AGENCY: United States NIEHS

GRANT: R01 ES 012451

ACRONYM: ES

MEDLINETA: Environ Health Perspect

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