Disease relevance of CASP3

• This results in damage to the mitochondria, with initiation of a membrane permeability transition and a decline in membrane potential, followed by release of cytochrome c, caspase 3 activation, and cellular toxicity [1].
• In a nephrotoxic nephritis (NTN) model, we previously demonstrated an up-regulation of caspase-3 that was associated with inappropriate renal apoptosis, inflammation, tubular atrophy, and renal scarring [2].
• Caspase-3-like-activities induced by the combination of DMSO or Na-butyrate with IFN-alpha were analyzed by gel filtration and detected equally in fractions with molecular weights of 200-300 kDa, suggesting that caspase-3 is activated in large complexes in lung cancer cells [3].

High impact information on CASP3

• There was release of mitochondrial cytochrome c into the cytosol and activation of caspase 3, which were prevented by cyclosporine, diallylsulfide, and Trolox [1].
• Caspase 3 increased more slowly, particularly in crypt epithelial cells (t(1/2) 57 (14.5) hours) [4].
• Caspase-8 played important roles in the activation of caspase-3 and induction of apoptosis, whereas the role of the caspase-9 was limited [5].
• Caspase 3 also peaked at 24 h in both the inner nuclear and outer nuclear layers and was predominantly expressed in photoreceptor cells and to a lesser extent in amacrine neurons [6].
• Cytofluorimetric and immunofluorescence data demonstrated the activation of caspase-3 and the involvement of mitochondria [7].

Biological context of CASP3

• Lastly, a pan caspase inhibitor (Z-D-DCB) and 2'-deoxycytidine (dCyd), which is known to prevent dGTP accumulation following PNP inhibition, were able to prevent cell death and all indicators of caspase-3-like activity in MOLT-4 cells co-treated with dGuo and CI-1000 [8].

Anatomical context of CASP3

• In summary, we provided several lines of evidence for the role of apoptosis and the contribution of caspase-3-like proteases in T-cell death following PNP inhibition [8].

Associations of CASP3 with chemical compounds

• Anti-PARP revealed the presence of an 85 kD PARP breakdown product while, anti-alpha-spectrin revealed the accumulation a 120 kD breakdown product, both suggestive of CPP32 cleavage (caspase-3; an ICE-like cysteine protease) [8].
• RESULTS: Cisplatin induced a dose-dependent increase in Caspase-3 activity and 8-fold of increase in apoptosis (p < 0.01) when applied for 24 h at 100 microM [9].

Analytical, diagnostic and therapeutic context of CASP3

• Western blots also detected the loss of the intact 32 kD caspase-3 isoform, a biochemical event associated with caspase-3 activation [8].

References