Molecular Mechanisms of Liver Injury and Hepatocarcinogenesis: Focusing on the Role of Stress-Activated MAPK

Figure 2

Signaling pathways of TNFα-induced hepatocyte death. After binding of TNFα to TNF-R1, complexes I and II are formed. As the amount of caspase-8 activation in complex II is not sufficient to induce cell death of hepatocytes, activation of the mitochondrial apoptotic pathway is essential. Activated caspase-8 initiates the mitochondrial apoptotic pathway by cleaving Bid to tBid. In addition, JNK can also activate the mitochondrial apoptotic pathway though modulation of Bcl-2 family members or degradation of c-FLIP. These pathways cooperate to induce cell death, while NF-κB and p38 inhibit TNFα-induced hepatocyte death by suppressing JNK activation through various mechanisms.