Apoptosis, inflammatory bowel disease and carcinogenesis: Molecular level (Part 5)

With regard to chronic intestinal inflammation, recent data indicate that increased production of cytokines (IL-12) prevent Fas-mediated T-cell apoptosis, resulting in T-cell accumulation in the gut. This mechanism of disease perpetuation can be successfully blocked by antibodies to IL-12.

In summary, the death-receptor pathway as typified by Fas (CD95/APO-1) includes the following. Oligomerization of Fas by FasL (on the same cell or a neighbouring one) causes recruitment of FADD to the cytoplasmic tail of Fas by their mutual DDs. The opposite end of FADD contains DEDs that allow recruitment of either procaspase 8 or FLICE inhibitory proteins. The latter contains a mutation in the enzymatic domain rendering it enzymatically inactive. Caspase 8 can cleave the BH3-only protein, Bid, and the resulting truncated Bid can inactivate Bcl-2 in the mitochondrial membrane (as can Bax following DNA damage).

This allows the escape of Cyt c, which clusters with Apaf-1 and caspase 9 in the presence of dATP to activate the caspase 9. Second mitochondria-derived activator of caspases/direct IAP-binding protein with low pI is also released from the mitochondria and inactivates IAPs. Active caspase 9 can cleave and activate procaspase 3 to its active form, resulting in activation of other caspases, breakdown of several cytoskeletal proteins and degradation of the caspase-activated DNase inhibitor, thereby releasing caspase-activated DNase that leads to DNA degradation, cell death and phagocytosis of cell debris. Visiting an online pharmacy has never been easier and safer, since now you have the one you can call your favorite one: buy female viagra online *here at the pharmacy that always takes care of its customers and always pay less money.


Category: Apoptosis

Tags: Apoptosis, Carcinogenesis, Caspases, Inflammatory bowel disease

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