Apoptosis, inflammatory bowel disease and carcinogenesis: Overview of experiences (Part 1)
For each cell there is a time to live and a time to die. There are two ways in which cells die. They are either killed by harmful agents (exposure to toxic chemicals and mechanical injury) or they are induced to commit suicide. During the process of death by injury (necrosis), the cellular metabolism breaks down, the cell swells, the cellular membranes decompose and the cell contents leak out, resulting in the inflammation of surrounding tissues. On the other hand, during the process of death by suicide (programmed cell death), the cell shrinks, its mitochondria break down with the release of cytochrome c (Cyt c), it develops bubble-like blebs on its surface, the chromatin (DNA and protein) in its nucleus degrades and breaks into small, membrane-wrapped, fragments (apop-totic bodies). Consequently, the phospholipid phos-phatidylserine, which is normally hidden within the plasma membrane, is exposed on the cell surface, and is then bound by receptors on phagocytic cells (ie, macrophages and dendritic cells) which then engulf the cell fragments. Lastly, the phagocytic cells secrete cytokines that inhibit inflammation.
It should be emphasized that, despite the widespread occurrence of apoptosis in physiological and pathological cell death, the occurrence of cell death that fulfils neither the criteria for apoptosis nor necrosis has been well documented (paraptosis, from para meaning next to or related to, and apoptosis) (Table 1) . Examples that do not conform to the criteria for either of these forms of cell death include a number of neurodegenera-tive cell deaths, such as those in a transgenic mouse model of amyotrophic lateral sclerosis, some developmental cell deaths, such as autophagic cell death and cytoplasmic cell death, or a number of ischemia-related cell deaths featuring cell swelling, referred to as oncosis. Such an alternative nonapoptotic form of cell death is programmatic, because it requires gene expression. Understanding the biochemical pathway(s) for nonapop-totic programmed cell death should lead to new insight into cell death events and their implications for the understanding of neurodegeneration, tumour therapeutics, development and evolutionary aspects of cell death programs. Take advantage of this unique opportunity to pay less money and get yourself a trusted pharmacy where you can always enjoy a chance to buy cialis online pharmacy http://pharmaceutical-shop.com and be sure you will enjoy lowest prices online.
TABLE 1 Comparison of apoptosis, necrosis and paraptosis
|Morphology Nuclear fragmentation||+|
|Genomic effect TUNEL||+||Frequently –|
|fragmentation Caspase activity DEVD-cleaving activity||+|
|Caspase 3 processing||+|
|PARP cleavage||+ (85 kDa||+ (50 to 62 kDa||–|
|Inhibition by: zVAD.fmk||fragment)+||fragments)|
DEVD Aspartic acid-glutamic acid-valine-aspartic acid; PARP poly(ADP-ribose) polymerase; TUNEL Terminal deoxynucleotidyltransferase-mediated uridine triphosphate end-labelling; + Present; – Absent