OBJECTIVES Activation of the caspase cascade through the mitochondrial and/or death receptor pathway was investigated in the failing human myocardium, in which the mode and extent of the cascade activation are unknown. BACKGROUND In terminal heart failure, a loss of cardiomyocytes by overload-induced apoptosis is an attractive mechanism, explaining the progressive character of the disease. Ho...

To detect caspase activities in intact apoptotic cells at the single cell level, cell-permeable fluorogenic caspase substrates were synthesized incorporating the optimal peptide recognition motifs for caspases 1, 3/7, 6, 8, and 9. Caspase activities were then assessed at various times after in vitro treatment of mouse thymocytes with dexamethasone or anti-Fas antibody. Dexamethasone induced the...

Irofulven (hydroxymethylacylfulvene) is a novel antitumor drug, which acts by alkylating cellular macromolecular targets. The drug is a potent inducer of apoptosis in various types of tumor cells, whereas it is nonapoptotic in normal cells. This study defined molecular responses to irofulven involving mitochondrial dysfunction and leading to death of prostate tumor LNCaP-Pro5 cells. Irofulven c...

Pemphigus vulgaris is a chronic, life-altering bullous autoimmune disease with production of antibodies against the desmosomal proteins Desmogleins 3 and 1 (Dsg) causing acantholysis. Ubiquitous antibody deposition but discontinuous manifestation indicate possible role cofactors. In this study, we focus on FasL as putative cofactor in PV-related To study cell-death dependent processes during PV...

Recent studies support the hypothesis that Alzheimer disease (AD)-associated amyloid-beta protein (Abeta) may induce apoptosis mediated by a caspase cascade. To assess whether mRNA levels of caspase-3, 7, 8 and 9 change in AD brain, and whether these changes correlate with neurofibrillary tangles, Abeta40 or Abeta42 protein levels or senile plaques, 25 AD and 21 non-demented control brains were...

Previous studies of thymocyte apoptosis using a series of cell-permeable fluorogenic peptide substrates showed that Fas cross-linking triggered a caspase cascade in which cleavage of the IETDase (caspase 8-selective) substrate was the earliest caspase activity measured by flow cytometry. This result was expected in light of the abundant evidence for caspase 8 activation as an initiating event i...

background: modulation of the immune response is an important strategy by which establish­ment and growth of hydatid cyst in the internal organs of human is warranted. induction of apop­tosis in the lymphocytes might be a considerable component. this study was designed to evaluate apoptotic impact of hydatid fluid (hf) on human lymphocytes. methods: human lymphocytes were treated with hydatid f...

Prostaglandin F(2alpha) (PGF(2alpha)) acting via a G protein-coupled receptor has been shown to induce apoptosis in the corpus luteum of many species. Studies were carried out to characterize changes in the apoptotic signaling cascade(s) culminating in luteal tissue apoptosis during PGF(2alpha)-induced luteolysis in the bovine species in which initiation of apoptosis was demonstrable at 18 h af...

Hormi-Carver K, Feagins LA, Spechler SJ, Souza RF. All trans-retinoic acid induces apoptosis via p38 and caspase pathways in metaplastic Barrett’s cells. Am J Physiol Gastrointest Liver Physiol 292: G18–G27, 2007. First published August 24, 2006; doi:10.1152/ajpgi.00237.2006.—Retinoids such as all trans-retinoic acid (ATRA) have been used as chemopreventive agents for a number of premalignant c...

We report here the purification of the third protein factor, Apaf-3, that participates in caspase-3 activation in vitro. Apaf-3 was identified as a member of the caspase family, caspase-9. Caspase-9 and Apaf-1 bind to each other via their respective NH2-terminal CED-3 homologous domains in the presence of cytochrome c and dATP, an event that leads to caspase-9 activation. Activated caspase-9 in...