Insulin-like growth factor-binding protein (IGFBP)-3 has been shown to potently inhibit cell proliferation in various cell systems. However, the specific mechanisms involved in the antiproliferative action of IGFBP-3 have yet to be elucidated. In the present study, we demonstrate that IGFBP-3 induces apoptosis in an insulin-like growth factor (IGF)-independent manner through the activation of c...

OBJECTIVE The effects of statins (3-hydroxy-3-methylglutaryl coenzyme A reductase-HMGR-inhibitors) on the inflammatory response remain unclear. HMGR is implicated in the mevalonate pathway, directly upstream of cholesterol biosynthesis. We studied the impairment by this pathway of cytokine production by peripheral blood mononuclear cells (PBMCs) and THP-1 cells. The aim was to identify a specif...

Caspases are cysteine-aspartic proteases that post-translationally modify their substrates through cleavage at specific sites, which causes either substrate inactivation or a gain of function through the generation of active fragments. Currently, each caspase is categorized as either an initiator of apoptosis or an end-stage executioner. Caspase-6 was originally identified as an executioner cas...

The present study was undertaken to gain insights into the molecular mechanism of cell death (apoptosis) by guggulsterone, a constituent of Ayurvedic medicinal plant Commiphora mukul, using PC-3 human prostate cancer cells as a model. The viability of PC-3 cells, but not a normal prostate epithelial cell line (PrEC), was reduced significantly on treatment with guggulsterone in a concentration-d...

We recently demonstrated that reperfusion rapidly induces the mitochondrial pathway of apoptosis in chick cardiomyocytes after 1 h of simulated ischemia. Here we tested whether ischemia-reperfusion (I/R)-induced apoptosis could be initiated by caspase-dependent cytochrome c release in this model of cardiomyocyte injury. Fluorometric assays of caspase activity showed little, if any, activation o...

Caspases are cysteine proteases that are key effectors in apoptotic cell death. Currently, there is a lack of tools that can be used to monitor the regulation of specific caspases in the context of distinct apoptotic programs. We describe the development of highly selective inhibitors and active site probes and their applications to directly monitor executioner (caspase-3 and -7) and initiator ...

Cytotoxic T lymphocytes (CTL) induce apoptosis by engaging death receptors or by exocytosis of cytolytic granules containing granzyme (Gzm) proteases and perforin. The lamins, which maintain the structural integrity of the nuclear envelope, are cleaved by caspases during caspase-mediated apoptosis. Although death receptor engagement and GzmB activate caspases, CTL also induce apoptosis during c...

Caspases play an important role in the ability of animal cells to kill themselves by apoptosis. Caspase activity is regulated in vivo by members of three distinct protease inhibitor families, two of which, baculovirus p35 and members of the inhibitor of apoptosis (IAP) family, are thought to be caspase specific. However, caspases are members of the clan of cysteine proteases designated CD, whic...

We investigated the potential role of the ubiquitin proteolytic system in the death of cerebellar granule neurons induced by reduction of extracellular potassium. Inhibitors of proteasomal function block apoptosis if administered at onset of this process, but they do not exert such effect when added 2-3 hr later. The same inhibitors also prevent caspase-3 activity and calpain-caspase-3-mediated...

Norepinephrine (NE) induces endoplasmic reticulum (ER) unfolded protein response and reduces maturation and translocation of NE transporter to cell membrane via enhanced formation of reactive oxygen species in PC-12 cells. In the present study, we investigated whether ER stress is also implicated in the proapoptotic effect of NE. We found that the apoptotic effect of NE was associated with incr...