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Deficiency in Ikk beta gene enhances arsenic-induced gadd45alpha expression.
Zhang Y; Lu Y; Ding M; Castranova V; Shi X; Chen F
Mol Cell Biochem 2005 Nov; 279(1-2):163-168
Chronic arsenic exposure is implicated in the pathophysiology of various human diseases, including cancer and diabetes. Using Ikkbeta gene knockout mouse embryonic fibroblast cells (Ikkbeta(-/-)), in the present study we demonstrated that NF-kappaB inhibition due to Ikkbeta deficiency up-regulated basal and arsenic-induced expression of gadd45alpha. In addition to gadd45alpha, the basal expression of other gadd family members including gadd45beta, gadd45gamma and gadd153 was substantially increased in Ikkbeta(-/-) cells. Ikkbeta deficiency prevented the induction of gadd45beta and gadd45gamma by arsenic, whereas the induction of gadd45alpha and gadd153 was appreciably enhanced in Ikkbeta(-/-) cells. Furthermore, a substantial decrease in the expression of c-myc, an established endogenous transcriptional repressor of gadd45alpha and gadd153 genes, was noted. Thus, these results uncover the molecular mechanism by which NF-kappaB signalling contributes to the regulation of gadd family gene expression induced by arsenic.
Arsenic-compounds; Chronic-exposure; Diseases; Cancer; Laboratory-animals; Animals; Animal-studies
F. Chen, Pathology and Physiology Research Branch, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV 26505, USA
Issue of Publication
Molecular and Cellular Biochemistry
Page last reviewed: August 5, 2022
Content source: National Institute for Occupational Safety and Health Education and Information Division