Proteases intracellular

Calpains are proteolytic enzymes with cysteine in the catalytic site. In general, calpains are found as intracellular proteases. These proteases are associated with many physiological basic processes of the cell. 

Jones K, Hoggard PC, Khoo S, Maher B, Back DJ (2001) Effect of alphal-acid glycoprotein on the intracellular accumulation of the HIV protease inhibitors saquinavir, ritonavir and indinavir in vitro, Br J Chn Pharmacol 51 99-102... 

APP is normally cleaved within the A/1 sequence by an unidentified protease, so-called a-secretase, so that most of the extracellular APP is released in a soluble form into the extracellular fluid (see Checler 1995). When jS-amyloid is formed another protease (jS) splits APP so that the complete A/1 sequence persists at the extracellular end of the remaining membrane and intracellular APP chain. This is then cleaved by anaother protease (y-secretase) to release the jS-amyloid (Fig. 18.5). Potentiation of a-or blockage of jS- and y-secretase could reduce the production of A/1 which becomes insoluble and is precipitated (see Hardy 1997). 

Injury to cells and tissues may enhance the toxicity of the active oxygen species by releasing intracellular transition metal ions (such as iron) into the surrounding tissue from storage sites, decompartmentalized haem proteins, or metalloproteins by interaction with delocalized proteases or oxidants. Such delocalized iron and haem proteins have the capacity to decompose peroxide to peroxyl and alkoxyl radicals, exacerbating the initial lesion. 

Bayot, A. Basse, N. Lee, I. Gareil, M. Pirotte, B. Bulteau, A. L. Friguet, B. Reboud-Ravaux, M. Towards the control of intracellular protein turnover mitochondrial Lon protease inhibitors versus proteasome inhibitors. Biochimie 2008, 90, 260-269. 

Antiapoptotic proteins. There are many different intracellular proteins that can prevent apoptosis by inhibiting specific steps in the cell death process. These include Bcl-2 family members such as Bcl-2 and Bcl-xL which can stabilize (mitochondrial, ER and plasma) membranes (Bcl-2 may also have intrinsic antioxidant activity). Other proteins, IAPs such as XIAP (X-linked) and NIAP (neuronal), which can directly inhibit caspases [31]. Additional examples of antiapoptotic proteins include protease inhibitors such as calpastatin, and protein chaperones such as GRP-78 and heat shock protein (HSP)-70. 

De Strooper, B., Annaert, W. G., Cupers, P. et al. A presenilin-1 -dependent gamma-secretase-like protease mediates release of Notch intracellular domain. Nature 398 518-522,1999. 

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