We describe the isolation and characterization of a new apaf-1-interacting protein (APIP) as a negative regulator of ischemic injury. APIP is highly expressed in skeletal muscle and heart and binds to the CARD of Apaf-1 in competition with caspase-9. Exogenous APIP inhibits cytochrome c-induced activation of caspase-3 and caspase-9, and suppresses cell death triggered by mitochondrial apoptotic...

NF-κB: nuclear factor κB; TNF-α: tumor necrosis factor α; DD: death domain; FADD: Fas-associated death domain; FasL: Fas receptor ligand; TNFR: TNF receptor; TRADD: TNFR-associated death domain; TRAF: TNFR-associated factor; COX: cyclooxygenase; PG: prostaglandin; iNOS: inducible nitric oxide synthase; NO: nitric oxide; MDR-1: multiple drug resistance gene; IL: interleukin; EGF: epithelial grow...

cell death could be an ideal solution for controlling and reducing tumor volume [8]. Numerous proteins are involved in apoptosis and thus serve as both potential targets as well as therapeutic tools in cancer treatment. A crucial event during apoptosis is the release of intra-mitochondrial pro-apoptotic proteins into the cytosol, which marks the point of no return in the process [9]. One of the...

The Apaf-1 protein is essential for cytochrome c-mediated caspase-9 activation in the intrinsic mammalian pathway of apoptosis. Although Apaf-1 is the only known mammalian homologue of the Caenorhabditis elegans CED-4 protein, the deficiency of apaf-1 in cells or in mice results in a limited cell survival phenotype, suggesting that alternative mechanisms of caspase activation and apoptosis exis...

Apoptotic signaling defects both promote tumorigenesis and confound chemotherapy. Typically, chemotherapeutics stimulate cytochrome c release to the cytoplasm, thereby activating the apoptosome. Although cancer cells can be refractory to cytochrome c release, many malignant cells also exhibit defects in cytochrome c-induced apoptosome activation, further promoting chemotherapeutic resistance. W...

Antipyretic analgesics, taken in large doses over a prolonged period, cause a specific form of kidney disease, characterized by papillary necrosis and interstitial scarring. Epidemiological evidence incriminated mixtures of drugs including aspirin (ASA), phenacetin, and caffeine. The mechanism of toxicity is unclear. We tested the effects of ASA, acetaminophen (APAF, the active metabolite of ph...

The aim of the present study was to investigate whether an increase in cyclin-dependent kinase 2 (CDK2) activity is involved in apoptosis of human bladder cancer T24 cells induced by isoliquiritigenin (ISL). The viability of T24 cells was estimated using a sulforhodamine B assay. Cell morphological changes were examined using Hoechst 33258 staining. The apoptotic rate was determined by staining...