LAUSR

We read with interest the recent paper by Chen and coworkers who provided evidence for Nrf2 as a novel target for c-jun N-terminal kinase (JNK).1 Although we agree that JNK activation is a critical part of the signaling mechanism of acetaminophen (APAP) hepatotoxicity,2 we disagree with the conclusion that P-JNK phosphorylation of Nrf2 causing down-regulation of Nrf2-dependent antioxidant response element (ARE)-driven genes Nqo1, Gstα3, Gstm1 and Gstm5 is the critical mechanism by which JNK promotes APAP-induced cell death.1 First, although JNK appears to phosphorylate Nrf2 in vivo as early as 3-6 h after APAP administration, the effects of the JNK inhibitor SP600125 on expression of these proteins was not observed during the main injury phase (6 h) but only at 24 h, i.e. at the end of the injury phase.