Journal
JOURNAL OF APPLIED TOXICOLOGY
Volume 38, Issue 8, Pages 1071-1080Publisher
WILEY
DOI: 10.1002/jat.3616
Keywords
Arsenite; EGCG; Keap1; Nrf2; pro-oxidant; redox homeostasis
Categories
Funding
- Department of Science and Technology (WOS-A, Kiran Division) [SR/WOS-A/LS-50/2014]
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Arsenite (AsIII) is known for inducing severe oxidative stress and skin carcinogenesis. Contrastingly, phytochemical, epigallocatechin-3-gallate (EGCG) combats toxic insults. Our study focused on the effect of EGCG on redox status of AsIII-stressed normal human keratinocytes, HaCaT cells. EGCG (50m) increased the cell viability by 29% in AsIII (50m) insulted HaCaT cells but exhibited pro-oxidant activity by elevated expression of the oxidative stress markers. EGCG was effective not only in reducing AsIII-induced nuclear expression of Nrf2 and Nrf2Ser40 but also in increasing nuclear expression of Keap1 both at protein and mRNA level. EGCG did not have similar effects on all Nrf2 downstream targets. EGCG elevated expression of HO-1 and -GCL,showed no change in MRP1 but decreased superoxide dismutase, NAD(P)H dehydrogenase quinone 1 and glutathione S transferase activity in AsIII-treated HaCaT cells. EGCG along with AsIII caused decreased phosphorylation of Nrf2 at ser40 residue, which might have facilitated Keap1-mediated nuclear export and degradation of Nrf2 and paved the pro-survival signal for AsIII-insulted HaCaT cells. In conclusion, it might be indicated that EGCG in spite of inducing the pro-oxidant effect was effective in increasing the viability of AsIII-treated HaCaT cells by partially restoring the Nrf2/Keap1-mediated signaling axis. EGCG in spite of inducing pro oxidant effect was effective in increasing the viability of arsenite treated HaCaT cells by partially restoring the Nrf2/Keap1 mediated signaling axis. EGCG along with arsenite caused decreased phosphorylation of Nrf2 at ser40 residue which might have facilitated Keap1 mediated nuclear export and degradation of Nrf2 and paved the pro survival signal for arsenite-insulted HaCaT cells. Thus, even though the cells suffered oxidative stress, they were observed with better survivable efficacy against arsenite-induced toxicity.
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