Apoptosis, poly polymerase

Messmer, U.K. et al., Nitric oxide induced poly(ADP-ribose) polymerase cleavage in RAW264.7 macrophage apoptosis is blocked by Bcl-2, FEES Lett., 384, 162, 1996. 

CuvUlier, O., Rosenthal, D.S., Smulson, M.E. and Spiegel, S., 1998, Sphingosine 1-phosphate inhibits activation ofcaspases that cleave poly(ADP-ribose)polymerase and lamins during Fas- and ceramide-mediated apoptosis injurkat T lymphocytes,/. Biol. Chem. 273 2910-2916. 

C. M. Payne, C. Crowley, D. Washo-Stultz, M. Briehl, H. Bernstein, C. Bernstein, S. Beard, Ft. Holubec and J. Warneke, The stress-response proteins poly(ADP-ribose) polymerase and NF-kappaB protect against bile salt-induced apoptosis, Cell Death Dijfer., 1998, 5(7), 623. 

Kaufmann, S.H., Desnoyers, S., Ottaviano, Y., Davidson, N.E. and Poirier, G.G. (1991) Specific proteolytic cleavage of poly (ADP-ribose) polymerase an early marker of chemotherapy-induced apoptosis. Cancer Res., 53, 3976-3985. 

Calmodulin, poly(ADP-ribose)polymerase and p53 are targets for modulating the effects of sulfur mustard (Rosenthal et al, 2000). It was tested whether calmodulin mediates the mitoehondrial apoptotic pathway induced by SM in human keratinoeytes. Of the three human CaM genes, the predominant form expressed was CaMl. These results indicate that CaM, ealeineurin, and Bad also play a role in SM-induced apoptosis, and may therefore be targets for therapeutic intervention to reduce SM injury (Simbulan-Rosenthal et al, 2006). 

Broaddus VC, Yang L, Scavo LM, et al. 1997. Crocidolite asbestos induces apoptosis of pleural mesothelial cells Role of reactive oxygen species and poly (ADP-ribosyl) polymerase. Environ Health Perspect Suppl 105 1147-1152. 

Inactivation of DNA repair enzymes can also turn on apoptosis. A fascinating apoptotic process can result from stress or toxicity that culminates in genomic damage in the cell nucleus, triggered by a nuclear enzyme poly (ADP-ribose) polymerase... 

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. 

Li, X. and Darzynkiewicz, Z. (2000) Cleavage of poly(ADP-ribose) polymerase measured in situ in individual cells relationship to DNA fragmentation and cell cycle position during apoptosis. Exp. Cell Res. 255,125-132. 

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-... 

The account given above is only the briefest summary of the explosion of work on the mechanisms of effect of sulphur mustard that has been published during the past ten or so years. It is clear that Papirmeister s hypothesis linking DNA repair by poly(ADP-ribose) polymerase with a reduction in NAD+ and activation of the hexose monophosphate shunt and subsequent activation of proteases is still plausible. However, so is the apoptosis theory linking as it does with increases in intracellular calcium levels. It has also been shown that sulphur mustard can affect, directly or indirectly, components of the epidermal-basal lamina linkage system and this may explain the blistering effect of this chemical. However, some questions remain ... 

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