The enterobacterial pathogen Salmonella induces phagocyte apoptosis in vitro and in vivo. These bacteria use a specialized type III secretion system to export a virulence factor, SipB, which directly activates the host’s apoptotic machinery by targeting caspase-1. Caspase-1 is not involved in most apoptotic processes but plays a major role in cytokine maturation. We show that caspase-1–deficien...

Alternatively spliced isoforms of certain apoptosis regulators, such as Bcl-x, Ced-4, and Ich-1, have been shown to play opposing roles in regulating apoptosis. Here, we describe the identification of an endogenous alternatively spliced isoform of caspase-9, named caspase-9b, which lacks the central large subunit caspase domain. Caspase-9b is detectable in many cell lines by PCR and at the mRNA...

The mechanisms by which infections induce diaphragm dysfunction remain poorly understood. The purpose of this study was to determine which caspase pathways (i.e., the extrinsic, death receptor-linked caspase-8 pathway, and/or the intrinsic, mitochondrial-related caspase-9 pathway) are responsible for endotoxin-induced diaphragm contractile dysfunction. We determined 1) whether endotoxin adminis...

RATIONALE Endothelial injury is an initial mechanism mediating cardiovascular disease. OBJECTIVE Here, we investigated the effect of hyperhomocysteinemia on programed cell death in endothelial cells (EC). METHODS AND RESULTS We established a novel flow-cytometric gating method to define pyrotosis (Annexin V(-)/Propidium iodide(+)). In cultured human EC, we found that: (1) homocysteine and l...

Salvia chorassanica Bunge is one of the Iranian endemic species of Salvia. There is not any reported literature on S. chorassanica. This study was designed to examine the in-vitro anti-proliferative and proapoptotic effects of the methanol extract of S. chorassanica and its fractions on HeLa cell line. Cells were cultured in EX-CELL®, an animal free medium specially designed for HeLa cell line ...

We recently described the induction of noncanonical IL-1β processing via caspase-8 recruited to ripoptosome signaling platforms in myeloid leukocytes. Here, we demonstrate that activated NLRP3·ASC inflammasomes recruit caspase-8 to drive IL-1β processing in murine bone marrow-derived dendritic cells (BMDC) independent of caspase-1 and -11. Sustained stimulation (>2 h) of LPS-primed caspase-1-de...

Receptor interacting protein-2 (RIP2) is a caspase recruitment domain (CARD)-containing kinase that interacts with caspase-1 and plays an important role in NF-kappaB activation. Apoptosis-associated speck-like protein containing a CARD (ASC) is a PYRIN and CARD-containing molecule, important in the induction of apoptosis and caspase-1 activation. Although RIP2 has also been linked to caspase-1 ...

Caspase-8 activation promotes cell apoptosis but is also essential for T cell activation. The extent of caspase activation and substrate cleavage in these divergent processes remains unclear. We show that murine effector CD4(+) T cells generated levels of caspase activity intermediate between unstimulated T cells and apoptotic populations. Both caspase-8 and caspase-3 were partially activated i...

Autocatalytic activation of an initiator caspase triggers the onset of apoptosis. In dying cells, caspase-9 activation is mediated by a multimeric adaptor complex known as the Apaf-1 apoptosome. The molecular mechanism by which caspase-9 is activated by the Apaf-1 apoptosome remains largely unknown. Here we demonstrate that the previously reported 1:1 interaction between Apaf-1 caspase recruitm...

BACKGROUND The significance of caspase-1 in prostate cancer has recently been documented (Cancer Res 61: 1227-1232, 2001). In this study, we investigated the role of caspase-1 in radiation-induced apoptosis in order to identify the significance of this apoptotic initiator in radiation resistance. MATERIALS AND METHODS Caspase-1 was over-expressed in DU-145 prostate cancer cells (which have we...