Two major intracellular pathways cause apoptosis

Two major intracellular pathways cause apoptosis. (A) Binding of FasL to CD95 (Fas receptor) leads to recruitment and activation of procaspase 8, which subsequently activates caspase 3. Activated caspase 3 is responsible for induction of several events that lead to apoptosis. A second apoptotic pathway is initiated by leakage of cytochrome C from the mitochondria, which together with caspase 9 and APAF1 forms the apoptosome that can activate caspase 3. The integrity of the mitochondrial membrane is regulated by proteins of the Bcl-2 family, Bax and Bak being proapoptotic, Bcl-2 and Bcl-xl antiapoptotic. (B) Apoptosis resistance in ulcerative colitis results from overexpression of FLIP, leading to impairment of the caspase mediated pathway of apoptosis. The mitochondrial pathway is intact. (C) In contrast, in Crohn’s disease, Fas induced apoptosis is normal but the mitochondrial pathway is affected by an imbalance of pro- and antiapoptotic Bcl-2 family members. As a consequence, activation induced apoptosis of T cells is impaired.

Publication

T cell apoptosis and inflammatory bowel disease. (2004) M P Peppelenbosch, et al. Gut. 2004 Nov;53(11):1556-1558. Figure: F1. All organisms Drosophila melanogaster Homo sapiens

Disease mentions