Poly polymerase caspase cleavage

Boulares AH, Yakovlev AG, Ivanova V et al. Role of poly(ADP-ribose) polymerase (PARP) cleavage in apoptosis. Caspase 3-resistant PARP mutant increases rates of apoptons in transfected cells. J Biol Chem 1999 274 22932-22940. 

Piot, C.A., Martini, J.F., Bui, S.K., and Wolfe, C.L. 1999. Ischemic preconditioning attenuates ischemia/reperfusion-induced activation of caspases and subsequent cleavage of poly(ADP-ribose) polymerase in rat hearts in vivo. Cardiovasc. Res. 44 536-542. 

The activation of caspase-3 assessed by the cleavage of poly ADP-ribose polymerase (PARP), a caspase-3 substrate, was confirmed in flavone-treated cells. Ac-DEVD-FMK (an inhibitory peptide for caspase-3), but not Ac-YVAD-... 

Apoptosis (programmed cell death) is characterized by a complex series of biochemical changes that culminate in cell death without inflammation or swelling, which are signs of necrosis. Embryonic, fetal, and postnatal development involve cell death by apoptosis, which serves to eliminate excessive cell proliferation and migration. Apoptosis is initiated by a variety of external stimuli and molecular events such as oxidative stress, mitochondrial permeability transition, mitochondrial cytochrome c release, activation of caspase proteases, activation of endonucleases, transglutaminase activation, and poly(ADP-ribose) polymerase cleavage. 

Assay of cleavage of known intracellular caspases substrates (i.e., Poly ADP Ribose Polymerase)... 

The effector caspases (caspase-3, caspase-6, caspase-7) are responsible for the morphological and biochemical changes that mark apoptosis. Activation of the effector caspases occurs via cleavage of the proform by activated initiator caspases and often marks the point of no return for cell death. Substrates for effector caspases include the caspases themselves (autoactivation), cytoskeletal components (i.e., actin, fodrin, and cytokeratins), poly (ADP-ribose) polymerase (PARP), and nuclear matrix proteins like Lamin B. Detection of caspase-3 expression by immunohistochemistry has been studied extensively due to its apical position in the effector caspase cascade (7-9,11-16). As with the initiator caspases, it is important to determine which form of the enzyme is recognized by the spe-... 

Herc Z, Wang ZQ. Failure of Poly(ADP-ribose) polymerase cleavage by caspases leads to induction of necrrrsis and enhanced apoptosis. Mol Cell Biol 1999 19(7) 5124-5133. 

Germain, M., Affar, E.B., D Amours, D., Dixit, V.M., Salvesen, G.S., and Poirier, G.G., 1999. Cleavage of automodified poly(ADP-ribose) polymerase during apoptosis. Evidence for involvement of caspase-7. The Journal of Biological Chemistry. 274 28379-28384. 

Over expression of tumor suppressor gene bcI-2 plays an important role in cellular resistance to apoptosis caused by various factors (77). Lin et al have shown that over expression of anti-apoptotic Bcl-2 and Bc1-Xl proteins may play a role in the development of resistance to cancer therapy 18). Functional over expression of Bcl-2 has been reported to confer an anti-apoptotic potential in a variety of cell types. The role of Bcl-2 in epithelial cell-cycle control and in interactions with other cell-cycle regulators is not clearly understood. Its expression has been correlated with the hormone- and chemo-resistant phenotype in advanced prostate cancer 19). Granville et al have shown that overexpression of Bcl-2 in HL-60 cells prevented apoptosis-related events including caspase 3 and 6 activation, poly (ADP-ribose) polymerase cleavage by photodynamic therapy (20). Over expression of HER2 in estrogen receptor (ER)-positive human breast tumors has been associated with resistance to endocrine therapy. 

However, the mechanism by which apoptosis is induced has not been defined. As described in Sect. 2.3.4, the catalysis of polyamines produces H2O2 as a byproduct, suggesting that apoptosis may be, in part, due to oxidative stress [134]. Treatment with other polyamine analogs revealed that multiple apoptotic mechanisms were involved. Typical features of apoptosis including cytochrome c release, activation of caspase-3, and cleavage of poly(ADP-ribose) polymerase (PARP) occur after treatment of tumor cells. 

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