Programmed cell death

Programmed cell death is physiologically draining death of cells in a multicellular organism. This is usually used to remove unnecessary or deliberately obstructive cells for the development or survival of the organism.

The opposite to the programmed cell death represents the traumatic death of a cell (necrosis)

Survey

The programmed death of cells as their growth (cell proliferation ) for the self-regulation of a multicellular organism is essential. A failure or a reduction of programmed cell death may lead to tumor formation. Also, an increased rate of cell death can have negative effects, such as by the formation of degenerative diseases such as Huntington's disease or amyotrophic lateral sclerosis.

Especially in the immune system of programmed cell death plays an important role. To eliminate Cytotoxic T cells virus-infected or malignant cells through the induction of programmed cell death. And in the maturation of T - lymphocytes and B- lymphocytes are potentially autoreactive cells, ie Cells that would attack the body's own tissues are removed by programmed cell death. Faults or errors can have such as multiple sclerosis or rheumatoid arthritis result in autoimmune diseases. Furthermore, after a successful immune response activated T cells, which are no longer required, are removed by programmed cell death.

Programmed cell death was described in 1842 in the observation of the ontogeny of vertebrates for the first time. Carl Vogt observed that are specifically degraded during the development of amphibians unwanted tissue, such as tail or webbed, by cell death. This "normal" cell death was soon demonstrated in the ontogeny of other vertebrates and invertebrates ( invertebrate ). The often-used term apoptosis was introduced in 1972 and was meant to differentiate the natural cell death during ontogeny of the necrosis.

Types of programmed cell death

Apoptosis

→ Main article: Apoptosis

Apoptosis can be triggered by various stimuli. DNA damage by radiation or chemicals leads to apoptotic cell death in many cases. A withdrawal of survival, growth factors and cytokines can induce apoptosis.

In the cell enzymes called caspases are activated by the above-mentioned stimuli. Based on the place of initiation, the apoptosis can be divided into two types. Apoptosis of the type I is characterized by the death receptor -mediated initiation of the caspase cascade, and the direct activation of caspase -3 by caspase -8. The type II apoptosis is mediated mitochondrial contrast and leads to activation of caspase- ninth

In classical apoptosis occurs subsequently to shrinkage of the cytoplasm and nucleus. This, the cells actively pump ions, especially potassium ions outwards and contract their cytoskeleton. The chromatin in the nucleus condenses to compact and geometric shapes ( spherical, sickle- shaped) and disintegrates into fragments. Next are formed by active constriction, as Zeiose or blebbing ( German: about, blistering ') refers to membrane vesicles. After an externalization ( post- outer - displacement) of phosphatidylserine ( "eat me" signal) is the shrunken cell then eliminated by phagocytes. Through these processes, the cells are addressed and there are degraded, in contrast to necrosis, not to release the cell contents so that there is no inflammatory reaction is induced.

Caspase- independent programmed cell death

In the course of evolution may have developed a number of programmed cell death -promoting signaling pathways due to the increasing complexity and life span of the organisms. The involvement of caspases could now be reliably detected only in highly developed animal organisms, such as vertebrates, insects and nematodes up. Alternative caspase- independent forms of programmed cell death can still be found in more primitive organisms.

In freshwater polyp apoptosis and the expression of two caspase -3- homologous genes could be shown. In the bacterium Bacillus subtilis mother cell becomes active lysed after sporulation. Escherichia coli responds to excessive DNA damage with their degradation and shows such as Streptococcus pneumoniae, a programmed cell lysis. Also in eukaryotic unicellular programmed cell death could be described. As show Trypanosoma cruzi and Trypanosoma brucei rhodesiense, Dictyostelium discoideum and Tetrahymena thermophila some apoptotic characteristics such as cytoplasmic blebbing and vacuolation, DNA fragmentation, and chromatin condensation in response to environmental stress or extracellular signals. In yeast programmed cell death could be detected. They show the yeast apoptosis- like features such as DNA fragmentation and condensation, blebbing and externalization of phosphatidylserine.

For many proteins and protein domains, which have a function in cell death in modern cells, homologous proteins have been found in bacteria. It is significant that in the mitochondria of proapoptotic factors are located, the access to certain signals to the cytoplasm and trigger cell death. Of the mitochondrial protein AIF (apoptosis - inducing factor ) is stated that its overexpression causes a caspase- independent DNA degradation. The endonuclease G to be responsible in conjunction with other DNases for the caspase- independent DNA degradation as AIF. A different mechanism of action have Smac / DIABLO and the serine protease Omi/HtrA2. Inhibit anti-apoptotic proteins such as XIAP and other IAP proteins, thus permitting the activation of Apaf / cytochrome c and caspase complex 3rd Serine protease Omi/HtrA2 enhances the cell death by the protease activity. Omi/HtrA2 is homologous to the bacterial heat-shock protease HtrA2.

In plants, fungi and protozoa called metacaspases were and described in metazoans and the slime mold Dictyostelium discoideum the Paracaspasen. Whether these for caspase family members of proteins in the signaling pathways of programmed cell death have a meaning, is still the subject of research. But it has been shown that caspases have developed from the Paracaspasen.

Programmed cell death without the involvement of caspases in modern -day organisms are important. It was observed in the mammal in vivo in the negative selection of lymphocytes, in the degradation of the embryonic interdigital skins, wherein tumor necrosis factor (TNF )-mediated liver injury, and the cell death of chondrocytes. Also in the nervous system neuronal caspase- independent cell death has been described.

Nekroseartiger programmed cell death

The programmed cell death necrosis- described shapes, in which no or at best a stained chromatin condensation without geometric structures can be observed. Other features such as an externalization of phagocytosis markers can occur in variable proportions. Some forms of programmed cell death nekroseartigen also be referred to as a broken apoptosis. The classical apoptosis is initiated but blocked at the level of caspase activation. Then caspaseunabhängige signal paths are taken to kill the cell.