How to Protect Against Acetaminophen: Don't Ask for JUNK

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Presentation transcript:

How to Protect Against Acetaminophen: Don't Ask for JUNK Neil Kaplowitz, Mie Shinohara, Zhang-Xu Liu, Derick Han Gastroenterology Volume 135, Issue 4, Pages 1047-1051 (October 2008) DOI: 10.1053/j.gastro.2008.08.031 Copyright © 2008 AGA Institute Terms and Conditions

Figure 1 Two-hit model of acetaminophen (APAP) hepatotoxicity. The metabolism of APAP exposes mitochondria to a reactive metabolite (NAPQI), which sensitizes mitochondria to JNK. JNK is activated by oxidative stress derived from the mitochondria by oxidation of redox-sensitive inhibitory proteins either upstream in the MAP kinase cascade or downstream at the level of JNK. Activated JNK translocates to mitochondria where it leads to MPT and necrosis. Gst, glutathione S-transferase; Trx, thioredoxin. Gastroenterology 2008 135, 1047-1051DOI: (10.1053/j.gastro.2008.08.031) Copyright © 2008 AGA Institute Terms and Conditions