Apoptosis caspase 3 activation

Apoptosis Caspase activation Cell membrane changes Changes of caspase activity DNA... 

Caspases are intracellular proteases and cleave their substrate proteins specifically behind an aspartate residue. Caspases are normally present as inactive proenzymes. However, during apoptosis, caspase activation is induced by cleavage at specific internal aspartate residues. Activation of the initiator caspases by pro-apoptotic signals leads to proteolytic activation of the execution caspases, which cleave a set of vital proteins and thus initiate and execute the apoptotic degradation phase. A self-contained on-chip cell culture and pretreatment microdevice system has been developed for the screening of caspase-3 expression in apoptotic cells. 

Caspase-9 Apoptosis, caspase activation Cys-287 iNOS Decreased enzymatic activity Negative Mannick et al. 1999... 

Caspases. Table 1 Diseases associated with inappropriate caspase activation. Contribution of apoptosis (A) and inflammation (I) are indicated... 

ALT, alanine aminotransferase ASC, apoptosis-associated speck-like protei containing a CARD AST, aspartate aminotransferase CARD, caspase activation and recruitment domains CD, Crohn s disease COP, CARD-only protein DD, death domain DED, death effector domains DIABLO, direct LAP-binding protein with low pi... 

Mitochondrial permeability transition involves the opening of a larger channel in the inner mitochondrial membrane leading to free radical generation, release of calcium into the cytosol and caspase activation. These alterations in mitochondrial permeability lead eventually to disruption of the respiratory chain and dqDletion of ATP. This in turn leads to release of soluble intramito-chondrial membrane proteins such as cytochrome C and apoptosis-inducing factor, which results in apoptosis. 

Kruman 11, Nath A, Mattson MP (1998) HlV-1 protein Tat induces apoptosis of hippocampal neurons by a mechanism involving caspase activation, calcium overload, and oxidative stress. Exp Neurol 154(2) 276-288... 

Rehm, M., Dussmann, H., Janicke, R. U., Tavare, J. M., Kogel, D. and Prehn, J. H. (2002). Single-cell fluorescence resonance energy transfer analysis demonstrates that caspase activation during apoptosis is a rapid process. Role of caspase-3. J. Biol. Chem. 277, 24506-14. 

Gurtu, V., Kain, S. R. and Zhang, G. (1997). Fluorometric and colorimetric detection of caspase activity associated with apoptosis. Anal. Biochem. 251, 98-102. 

Classic antioxidants, vitamin E, vitamin C, and others can suppress the activation of apoptosis. For example, ascorbic acid prevented cytochrome c release and caspase activation in human leukemia cells exposed to hydrogen peroxide [128], Pretreatment with A -acctylcystcinc, ascorbate, and vitamin E decreased homocysteine thiolactone-induced apoptosis in human promyelocytic leukemia HL-60 cells [129]. Resveratrol protected rat brain mitochondria from anoxia-reoxygenation damage by the inhibition of cytochrome c release and the reduction of superoxide production [130]. However, it should be mentioned that the proapoptotic effect of ascorbate, gallic acid, or epigallocatechin gallate has been shown in the same human promyelocytic leukemia cells [131]. 

The postmitochondrial events of apoptosis include activation of the caspases 610... 

Many of the morphological and biochemical changes that occur in cells that die by necrosis are very different from those that occur in apoptosis. During necrosis cells swell, mitochondria and endoplasmic reticulum lose their structure and become dysfunctional and the nuclear membrane becomes disrupted (Fig. 35-1). Necrotic death is independent of premitochondrial apoptotic proteins such as Bax, cytochrome c release and caspase activation. Necrosis is further distinguished from apoptosis by the fact that necrosis usually occurs as the result of a traumatic physical injury or stroke and cells die en masse, whereas apoptosis typically occurs in individual cells within a population of surviving neighbors. 

Fas ligand and interleukin-ip), the neurotransmitter glutamate and thrombin. Like tumor necrosis factor (TNF) receptors, Fas is coupled to downstream death effector proteins that ultimately induce caspase activation (Ch. 22). Fas and TNF receptors recruit proteins called FADD and TRADD respectively FADD and TRADD then activate caspase-8, which, in turn, activates caspase-3 (Fig. 35-4). Calcium ion influx mediates neuronal apoptosis induced by glutamate receptor activation calcium induces mitochondrial membrane permeability transition pore opening, release of cytochrome c and caspase activation. Interestingly, in the absence of neurotrophic factors some neurotrophic factor receptors can activate apoptotic cascades, the low-affinity NGF receptor being one example of such a death receptor mechanism [23],... 

The postmitochondrial events of apoptosis include activation of the caspases. Cytochrome c binds to the protein Apaf-1 in the cytosol, resulting in the recruitment and activation of caspase-9, which in turn activates cas-pase-3 (Figs 35-4, 35-5). Fourteen different mammalian caspases have been identified and each may play a key role... 

Miura, K., Aminova L., and MurayamaY. Fusarenon-X induced apoptosis in HL-60 cells depends on caspase activation and cytochrome c release. Toxicology 172, 103, 2002. 

Byrd, J., Kitada, S., Flinn, L, Aron, J., Pearson, M., Lucas, D., and Reed, J.C., The mechanism of tumor cell clearance by rituximab leukemia evidence of caspase activation and apoptosis induction. Blood, 99, 1038-1043, 2002. 

Park, E.-J., Zhao, Y.-Z., Kim, J., and Sohn, D. H. (2006). A ginsenoside metabolite 20-O-P-D-glucopyranosyl-20(S)-protopanaxadiol, triggers apoptosis in activated rat hepatic stellate cells via caspase-3 activation. Planta Med. 11,1250-1253. 

The toxic effect of 7-oxysterols, 25- and 27-hydroxycholesterols and their involvement in LDL cytotoxicity have been extensively studied on the different vascular cell types (Lizard et al, 1999 Aupeix et al, 1995 Clare et al, 1995 Ramasamy et al, 1992). 7a and 7p-hydroxycholesterols, 7-ketocholesterol, 25 and 27-hydroxycholesterol induce apoptosis (Brown and Jessup, 1999 Lizard et al, 1999, 1998 Zhang et al, 1997 Hughes et al, 1994). 7p-hydroperoxycholesterol is one of the most toxic Oxysterols present in oxidized LDL (Brown and Jessup, 1999 Colles et al, 1996). 25-hydroxycholesterol, though less active (Aupeix et al 1995), is able to trigger a cytochrome c release and subsequent caspase activation in CHO cells, but also calcium inaease in relation with apoptosis (Rusinol et al, 2000). 

Their role in oxidized-mediated cell death is also assessed (i) by the protective effect of antioxidants which reduce or inhibit oxidized LDL-induced ROS generation, caspase activation and subsequent apoptosis. 

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