Advance research in apoptosis mediating by death receptor

Apoptosis is one of the main types of programmed cell deaths(PCD)and involves a series of biochemical events that lead to a variety of morphological changes and death.The initial and progress of apoptosis is precisely regulated.This review will summarize current knowledge of the signal transduction pathways of apoptosis.It is now well-established that the apoptotic signals generally involve the extrinsic or intrinsic pathways of apoptosis.The extrinsic pathway originates at the membrane and engages cell surface receptors whereas the intrinsic pathway predominantly involves mitochondria.In the intrinsic pathway,the cell signal induced changes of mitochondrial membrane permeability and the loss of membrane potential.Many proteins factors released,and then cytoplasmic cytochrome C and caspase-9 form of apoptosis.The activated caspase-9 cut caspase-3,then cell dead at last.In the case of extrinsic pathway,several receptors exist including Fas,TNFR-1,DR3,DR4,DR5 and DR6.These receptors contain an intracellular region of approximately 80 amino acids that is designated as death domain.The domain is an important structure that plays a key role in the transduction of apoptotic signals.The interaction between Fas and its ligand(FasL)triggers the formation of a death-inducing signaling complex(DISC),which subsequently recruits and activates caspase-8;this in turn activates other procaspases and culminates in the cleavage of cellular substrates and apoptosis.During the process of tumor cell lines apoptosis Inducted by chemotherapy.It is easy to see the increasing of the Fas receptors and inducing of FasL expression,it can inhibite apoptosis when the blocking Fas /FasL.Tumor necrosis factor(TNF)-related apoptosis-inducing ligand(TRAIL)is a type II transmembrane protein belonging to the TNF family of ligands.TRAIL has been suggested as a safe and tumorselective anticancer agent with low toxicity to normal tissues,and is thought to play a role in tumor immune surveillance by NK,T cells and probably also cells of the innate immune system.The interaction between TNF and its ligand(TRAIL)recruits and activates caspases,TRAIL transmitting the signals through FADD,the probable mechanism is that:activated TRAIL combined with FADD through mutual recognition of Death domain,FADD combined MACH/FLICE(caspase-8),and then activates ICE/CED3 of caspase-8 and other proteins.The vast majority of cancer chemotherapy drug,mainly play a role through mitochondria-induced apoptosis pathway.TRAIL-induced apoptosis rely on the activation of caspase-8 and caspase-3.The mitochondrial membrane potential was reducted and the cytochrome C was released,leading to no damage of mitochondrial integrity after DNA cracking.Caspase is a specific type of acid cysteine protease,in apoptosis directly involved in the process of implementing the early start of apoptosis,signal transduction and apoptosis of late.Caspase-8 plays a key role in the receptor-mediated apoptosis.