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The oncogenic protein Bcl-2 which is expressed in membranes of different subcellular organelles protects cells from apoptosis induced by endogenic stimuli. Most of the results published so far emphasise the importance of Bcl-2 at the mitochondria. Several recent observations suggest a role of Bcl-2 at the endoplasmic reticulum (ER). Bcl-2 located at the ER was shown to interfere with apoptosis induction...
Functional role of peripheral benzodiazepine receptor on mitochondrial membrane in apoptosis and insulin secretion from insulinoma cells was studied. A prototypic peripheral benzodiazepine receptor agonist PK11195 induced insulinoma cell apoptosis, while a central benzodiazepine receptor agonist did not. Death of insulinoma cells by PK11195 was inhibited by cyclosporin A,{ a blocker of mitochondrial...
Accumulation of beta-amyloid (Aβ) peptides in senile plaques is one of the pathological hallmarks in Alzheimer's disease (AD), which can trigger apoptosis. We have previously demonstrated that Aβ triggered calcium release from the ER. Depletion of ER Ca2+ ions has been reported leading to unfolded protein responses (UPR). While hypothesis has been made about UPR and neurodegeneration in AD, little...
Triterpenoids are a novel class of compounds being investigated as potential therapeutic agents for the treatment of prostate cancer and other malignancies. Asiatic acid (AA) is a member of the ursane family of triterpenoids and has anticancer activity, but its mechanism of action is not completely understood. To investigate its mechanism of action, PPC-1 prostate cancer cells were treated with AA...
Aristolochic acid (AA) has been demonstrated to play a causal role in Chinese herbs nephropathy. However, the detailed mechanism for AA to induce apoptosis of renal tubular cells remains obscure. In this study, we show that AA evokes a rapid rise in the intracellular Ca2+ concentration of renal tubular cells through release of intracellular endoplasmic reticulum Ca2+ stores and influx of extracellular...
Inositol 1,4,5-trisphosphate receptors (IP3Rs) serve to discharge Ca2+ from ER stores in response to agonist stimulation. The present review summarizes the role of these receptors in models of Ca2+-dependent apoptosis. In particular we focus on the regulation of IP3Rs by caspase-3 cleavage, cytochrome c, anti-apoptotic proteins and Akt kinase. We also address the evidence that some of the effects...
One hallmark of programmed cell death (PCD) is redistribution of phosphatidylserine (PS) to the plasma membrane’s outer leaflet. Annexin V is widely used in cell death research due to its calcium-dependent ability to bind phosphatidylserine, thus marking apoptotic cells. However, calcium is invariably used at high concentrations in annexin V staining, at doses that can induce cell death. We used flow...
The very early events of the intrinsic, damage-induced apoptotic pathway, i.e., upstream to Bax activation, probably consist of physico-chemical alterations (i.e., redox, pH or Ca2+ changes) rather then subtle molecular interactions, and in spite of many studies they remain unclear. One problem is that cells undergo apoptosis in an asynchronous way, leading to heterogeneity in the cell population...
We investigated the effect of the novel phospholipase C activator, m-3M3FBS, on the apoptosis of human renal Caki cancer cells. Treatment with m-3M3FBS induced apoptosis of Caki cells, which was accompanied by accumulation of sub-G1 phase and DNA fragmentation. We found that induction of apoptosis is a common response of several cancer cell types to m-3M3FBS treatment. Overexpression of Bcl-2 and...
The aim of this study was to examine whether, a new synthesized class of benzocycloalkene derivatives (BCs), enhances apoptosis induced by hyperthermia. The combined effects of hyperthermia (44°C, 20 min) and BCs on apoptosis in human lymphoma U937 cells were investigated. Among the tested compounds (BC1 ∼ 9), the combined treatment of 10 μM BC2 or BC4 and hyperthermia showed the largest potency to...
Sanazole has been tested clinically as a hypoxic cell radiosensitizer. In this study, we determined whether sanazole enhances the radiation-induced apoptosis of human lymphoma U937 cells. Our results revealed that, compared with 10 mM sanazole or radiation alone, the combination of both resulted in a significant enhancement of apoptosis after 6 h, which was evaluated on the basis of DNA fragmentation,...
Apoptosis is defined by specific morphological and biochemical characteristics including cell shrinkage (termed apoptotic volume decrease), a process that results from the regulation of ion channels and plasma membrane transporter activity. The Na+–K+-ATPase is the predominant pump that controls cell volume and plasma membrane potential in cells and alterations in its function have been suggested...
Hyperosmotic stress promotes rapid and pronounced apoptosis in cultured cardiomyocytes. Here, we investigated if Ca2+ signals contribute to this response. Exposure of cardiomyocytes to sorbitol [600 mosmol (kg water)−1] elicited large and oscillatory intracellular Ca2+ concentration increases. These Ca2+ signals were inhibited by nifedipine, Cd2+, U73122, xestospongin C and ryanodine, suggesting contributions...
The structure and function of the mitochondrial network is regulated by mitochondrial biogenesis, fission, fusion, transport and degradation. A well-maintained balance of these processes (mitochondrial dynamics) is essential for neuronal signaling, plasticity and transmitter release. Core proteins of the mitochondrial dynamics machinery play important roles in the regulation of apoptosis, and mutations...
Panaxydol, a polyacetylenic compound derived from Panax ginseng roots, has been shown to inhibit the growth of cancer cells. In this study, we demonstrated that panaxydol induced apoptosis preferentially in transformed cells with a minimal effect on non-transformed cells. Furthermore, panaxydol was shown to induce apoptosis through an increase in intracellular Ca2+ concentration ([Ca2+]i), activation...
Stimuli directed towards activation of apoptosis mechanisms are an attractive approach to eliminate evasion of apoptosis, a ubiquitous cancer hallmark. In these in vitro studies, kinetics and electric field thresholds for several apoptosis characteristics are defined in E4 squamous carcinoma cells (SCC) exposed to ten 300 ns pulses with increasing electric fields. Cell death was >95% at the highest...
Perturbation of cellular K+ homeostasis is a common motif in apoptosis but it is unknown whether a decrease in intracellular K+ alone is sufficient to replicate apoptotic hallmarks. We investigated, which mode of cell death is induced by decreasing the intracellular K+ concentration using valinomycin, a highly K+-selective ionophore. Valinomycin treatment induced mitochondrial swelling and minor nuclear...
Apoptosis, necrosis and autophagy are mechanistically related processes that control tissue homeostasis and cell survival. In the testis, germ cell death is important for controlling sperm output, but it is unknown whether or not germ cells can switch from apoptosis to necrosis, as has been reported in other tissues. Furthermore, autophagy has not been reported in spermatogenesis. Spermatocytes (meiotic...
The irradiation of fat-containing food forms 2-dodecylcyclobutanone (2-DCB) from palmitic acid (PA). In this study, we investigated whether 2-DCB and PA induce apoptosis in human lymphoma U937 cells. We found that cell viability decreased by 2-DCB and apoptosis was induced by 2-DCB and PA. 2-DCB and PA significantly enhanced the formation of intracellular reactive oxygen species (ROS). Apoptosis induced...
The persistent xenobiotic agent 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces neurotoxic effects that alters neurodevelopment and behavior both during development and adulthood. There are many ongoing efforts to determine the molecular mechanisms of TCDD-mediated neurotoxicity, the signaling pathways involved and its molecular targets in neurons. In this work, we have used SHSY5Y human neuroblastoma...
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