**1. Introduction**

Apoptosis, as a programmed cell death (PCD) is essential for normal cell mechanism. The word "Apoptosis" derives from Greek language "απόπτωσις" and means trees shedding their leaves in autumn, which describes the "dropping off" or "falling off" of petals from flowers, or leaves from trees. This language imaginarily described the cell death triggered by physiological and pathological stimulation. The apoptosis phenomena were first described by German Scientist Carl Vogt in 1842 year, while until 1972 year, apoptosis term was first used by John Foxton Ross Kerr group. They use apoptosis word to describe the tissue cell death. The above is the beginning of apoptosis researches and this period is the apoptosis formation; the second period about apoptosis is the biochemical level and apoptosis cell morphological changes research. In this age, people know that apoptosis accompany with cell membrane wrinkled, DNA fragmentation, cytosol calcium increased and form the apoptosis body which contain its own content so on. In this time the electron microscope play a vital role in the research. Following the apoptosis research came in the third period in recent years; scientists began to research the molecular mechanism of apoptosis and to use this cell death for clinical treatment. Some key proteins in the procession of the apoptosis have been found, such as Bcl-2 family protein, caspase-3, caspase-8, caspase-9, Bid, Bax and so on.

In the past, the apoptosis was focused on the caspase, a family of cysteine protease. While, using the caspase inhibitor to block the apoptosis pathway, the researchers found that the apoptosis still happen. So another pathway that is caspase-independent was found. Now, apoptosis is classified to type I, Type II, Type III PCD: type I PCD is the classic apoptosis, the well know caspase denpendent apoptosis; type II PCD's morphology characters are the appearance of the autophagic and double membrane of vacuole; type III PCD occurs without the condensate chromatin and has not been well-known. Type IIand type III PCD are the caspase-independent apoptosis. For example, the apoptosis induce factor(AIF), a mitochondria intermembrane flavoprotein, that can be released from mitochondria to

© 2012 Hongmei, licensee InTech. This is an open access chapter distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2012 Hongmei, licensee InTech. This is a paper distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

translocate into the nuclear and cause many high molecular weight DNA fragmentation and chromatin condensation in cells, this type of apoptosis is in the caspase-independent manner. [65] No mater the typeI, Type II or type III PCD, the apoptosis will assist the host to defense the outer or inner aliens and toxic compounds and help the organism survive.

Extrinsic and Intrinsic Apoptosis Signal Pathway Review 5

fundamental apoptotic pathways and summarize many ligands that can trigger apoptosis and give some insights in the designing some drugs, plus, we also give the opinions that

Apoptosis is triggered by multi-signal pathways and regulated by multi-complicated extrinsic and intrinsic ligands. The process of apoptosis is controlled by diversity cell signals pathway and involved in regulation of cell fate death or survival. There are two major apoptosis pathways distinguished according to whether caspases are involved or not. The mitochondria, as the cross-talk organelles, can connect the different apoptosis pathway.

Caspase-dependent apoptosis is the classic programmed cell death pathway, the capase-8, caspase-9, caspase-12, caspase-7, caspase-3 cascade usually participate in this type of apoptosis pathway, Variety of receptors take part in this type of apoptosis pathway, such as the TNF-alpha receptor, FasL receptor, TLR, Death receptor and so on. Some iron channels may also be involved in apoptosis pathway. The typical iron channel is the calcium channel, Since calcium's concentration in the cytosol plays an important role in the signal transduction regulation and participates in the cell proliferation and cell death, the cell fate can be controlled by the calcium channel opening or closing. In this part, we will discuss the caspase-dependent apoptosis transduction and review the complex signal crosstalk in the

TNF-alpha induced caspase-8-dependent pathway relies on the TNF-alpha receptor and activates the caspase-8 through the death complex, and then the Bcl-2 protein is activated, Bcl-2 family protein activation may induced the mitochondria membrane changed and stimulates the cytochrome c released. Cytochrome c is the proapoptosis signal molecular which can activates the caspase cascade reaction and induced the apoptosis in the end. Some radiation UV or X ray can make mitochondria depolarization and membrane permeabilization, subsequently, the ROS increased; cytochorme c released, and then trigger caspase-9, caspase-3 activation,, In the end, the substracts will be cleavaged by the activation caspases and the fate of cells will be apoptosis; Some pathogen infection induced the apoptosis may be also have the caspase-8 dependent pathway, The alien pathogens can be recognized by FasL receptor and recruit FADD and caspase-8, for example, the intracellular pathogen herpervirus infection can induced the caspase-8 dependent apoptosis. Beside caspase-8 dependent apoptosis, some pathogens can trigger others caspases dependent apoptosis pathway. For example, Mycobacterium tuberculosis can induce programmed cell death on macrophage, and this apoptosis pathway is the caspase-12 dependent. NO and ROS production, stimulated by ER stress, also take part in apoptosis triggered by Mycobacterium tuberculosis; [1] Exclude bacteria, virus also can induce the apoptosis. The latest research found that an alternative Kaposi's sarcoma-associated herpesvirus replication can trigger host cell apoptosis in caspase dependent manner. [2]. Apart

changes the dietary arable may be help to improve the people's healthy.

**3. Apoptosis signal pathway** 

**3.1. Caspase dependent pathway** 

cells.

In this chapter, we will key on the apoptosis signal pathway and some ligands have the clue with apoptosis and mainly on concluded the apoptosis on two aspects, from in vivo and in vitro cells, and we can clarify the network of this cell death and give the conclusion of the latest research about this.
