Title : Depletion of intracellular glutathione contributes to JNK-mediated death receptor 5 upregulation and apoptosis induction by the novel synthetic triterpenoid methyl-2-cyano-3, 12-dioxooleana-1, 9-dien-28-oate (CDDO-Me).

Pub. Date : 2006 May

PMID : 16582599






5 Functional Relationships(s)
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1 We previously demonstrated that CDDO-Me induces a c-Jun N-terminal kinase (JNK)-mediated DR5 expression and apoptosis. bardoxolone methyl TNF receptor superfamily member 10b Homo sapiens
2 This study revealed the mechanism by which CDDO-Me induces JNK activation and subsequent DR5 upregulation and apoptosis. bardoxolone methyl TNF receptor superfamily member 10b Homo sapiens
3 To determine whether CDDO-Me activates JNK and induces DR5 expression and apoptosis via oxidative stress by inducing the generation of reactive oxygen species (ROS), we examined the effects of various antioxidants on JNK activation, DR5 upregulation, and apoptosis induction by CDDO-Me. bardoxolone methyl TNF receptor superfamily member 10b Homo sapiens
4 Furthermore, these thiol antioxidants abrogated CDDO-Me-induced DR5 expression, whereas the GSH-depleting agent diethylmaleate also upregulated DR5 expression at concentrations that deplete intracellular GSH, demonstrating that GSH depletion can cause DR5 upregulation. bardoxolone methyl TNF receptor superfamily member 10b Homo sapiens
5 Collectively, we conclude that CDDO-Me activates the JNK pathway via depletion of intracellular GSH, leading to DR5 upregulation and induction of apoptosis. bardoxolone methyl TNF receptor superfamily member 10b Homo sapiens