Death Receptors

Abstract

Apoptosis, or programmed cell death, is a common property of all multicellular organisms and maintains essential cellular homeostasis in tissues by balancing cell renewal and removal of mutated or old cells. It can be triggered by a number of factors including ultraviolet (UV) or γ‐irradiation, chemotherapeutic drugs or growth factor withdrawal. A death signal can either be induced by the activation of death receptors (DRs, extrinsic pathway) or via the mitochondria (intrinsic pathway). The DR family is a subfamily of the tumour necrosis factor receptor (TNFR) superfamily. Stimulation of the DRs results in the formation of high‐molecular‐weight protein complexes that transduce apoptotic, necroptotic or survival signals. Key Concepts Stimulation of the death receptors (DRs) leads to apoptosis, necroptosis or NF‐κB activation. All DRs are distinguished by the presence of the death domain (DD). Cross‐linking of DR with death ligands results in the formation of the death‐inducing signalling complex (DISC). Caspases play the central role in the transduction of DR‐induced apoptotic signal. Procaspase‐8 is activated at the death effector domain (DED) chains at the DISC. c‐FLIP proteins block or promote caspase‐8 activation at the DISC depending on their amount at the receptor complex and thereby regulate DR‐induced apoptosis. Stimulation of DR might lead to the induction of receptor‐interacting protein kinase 1 and 3 (RIPK1‐ and RIPK3)‐mediated nonapoptotic cell death, necroptosis. Apoptosis and necroptosis are triggered by high‐molecular‐weight protein complexes consisting of similar proteins.

Effect and mechanism of Fisetin on myocardial damage induced by Patulin

“…When mitochondria sense the death signal, a cascade of Bcl-2 protein family is transmitted to Caspase-3 [24]. The membrane receptor pathway is also known as the death receptor pathway, and the main perception and transmission of extracellular death signals are classi ed according to different death receptor proteins [27]. In the caspase family, different caspase enzymes mediate different apoptotic signals.…”