The role of caspases and calpain in cisplatin-induced endothelial cell death is unknown. Thus we investigated whether caspases and calpain are mediators of cisplatin-induced apoptosis and necrosis in endothelial cells. Cultured pancreatic microvascular endothelial (MS1) cells were exposed to 10 and 50 microM cisplatin. Apoptosis or necrosis was determined by Hoechst 33342 and propidium iodide (...

Malignant gliomas are almost uniformly fatal and display exquisite radiation resistance. Glioma cells lacking wild-type (WT) p53 function are more susceptible to radiation-induced apoptosis than their isogenic counterparts expressing WT p53. We explored the mechanisms of such apoptosis and found that, in the absence of WT p53, radiation increases caspase8 expression and activity. Inhibition of ...

Caspase-2 is an evolutionarily conserved but enigmatic protease whose biological role remains poorly understood. To date, research into the functions of caspase-2 has been hampered by an absence of reagents that can distinguish its activity from that of the downstream apoptotic caspase, caspase-3. Identification of protein substrates of caspase-2 that are efficiently cleaved within cells may al...

A series of 11 new substituted 1,5-dihydro-4,1-benzoxazepine derivatives was synthesised to study the influence methyl group in 1-(benzenesulphonyl) moiety, replacement purine by benzotriazole bioisosteric analogue, and introduction a bulky substituent at position 6 purine, on biological effects. Their inhibition against isolated HER2 studied structure–activity relationships have been confirmed...

ceramide as a second messenger is a key regulator in apoptosis and cytotoxicity. ceramide-metabolizing enzymes are ideal target in cancer chemo-preventive studies. neutral sphingomyelinase (nsmase), acid ceramidase (acdase) and glucosyl ceramide synthase (gcs) are the main enzymes in ceramide metabolism. silymarin flavonolignans are potent apoptosis inducers and silibinin is the most active com...

objective(s):higher cellular reactive oxygen species (ros) levels is important in reducing cellular energy charge (ec) by increasing the levels of key metabolic protein, and nitrosative modifications, and have been shown to damage the cardiac tissue of diabetic mice. however, the relation between energy production and heart function is unclear. materials and methods:streptozotocin (stz, 150 mg/...

objective(s):in previous investigations, we have shown para-nonylphenol (p-np) caused significant reduction of proliferation and differentiation of rat bone marrow mesenchymal stem cells (mscs) in vitro. in this study, we first treat the rats with p-np, then carried out the biochemical and morphological studies on mscs. materials and methods: proliferation property of cells was evaluated with t...

objective(s): this study was designed to indicate whether different fractions from artemisia biennis hydroethanolic extract could provide cytoprotection against oxidative stress and apoptosis induced by doxorubicin (dox) in rat pheochromocytoma cell line (pc12). material and methods:cell viability was determined by mtt assay. also, activation of caspase-3 and superoxide dismutase were evaluated...

Caspase-3 cleavage and activation are known to play central roles in apoptosis. However, the mechanisms that regulate caspase-3 cleavage remain elusive. Glutaredoxin (Grx) is a ubiquitous redox molecule that is unique in its ability to regulate S-glutathiolation (glutathiolation) of proteins. Here we show the essential role of Grx in caspase-3 cleavage via regulation of caspase-3 glutathiolatio...

We have cloned and sequenced cDNAs corresponding to the complete coding regions of the chicken homologues to mammalian caspase-3 and caspase-6. Both caspases are included among members of the cysteine protease (caspase) family that are most closely identified with mediating apoptosis. The deduced amino acid sequences for chicken caspase-3 and -6 show 65% and 68% identity with the respective hum...