Interaction of RIPK1 and A20 modulates MAPK signaling in murine acetaminophen toxicity.

ABSTRACT: Acetaminophen (APAP)-induced liver necrosis is a form of regulated cell death (RCD) in which APAP activates the mitogen-activated protein kinases (MAPKs) and specifically the c-Jun-N-terminal kinase (JNK) pathway, leading to necrotic cell death. Previously, we have shown that receptor interacting protein kinase-1 (RIPK1) knockdown is also protective against APAP RCD upstream of JNK. However, whether the kinase or platform function of RIPK1 is involved in APAP RCD is not known. To answer this question, we used genetic mouse models of targeted hepatocyte RIPK1 knockout (RIPK1^HepCKO) or kinase dead knock-in (RIPK1^D138N) and adult hepatocyte specific knockout of the cytoprotective protein A20 (A20^HepCKO), known to interact with RIPK1, to study its potential inv

SUBMITTER: Iorga A 

PROVIDER: S-EPMC7948960 | biostudies-literature | 2021 Jan-Jun

REPOSITORIES: biostudies-literature