As a form of new programmed cell death, pyroptosis is divided into a canonical pyroptosis pathway and a non-canonical pyroptosis pathway. In recent years, it is reported that non-canonical pyroptosis is closely related to inflammatory reactions, which directly affects the occurrence, development, and outcome of sepsis, inflammatory bowel disease, respiratory disease, nerve system inflammatory disease, and other inflammatory diseases. When the cells were infected with Gram-negative bacteria or lipopolysaccharide (LPS), it can induce the activation of cysteinyl aspartate specific proteinase(caspase)-4/5/11 and directly bind to the cells to cleave gasdermin D (GSDM-D) into the active amino-terminus of GSDM-D. The amino-terminus of GSDM-D with membrane punching activity migrates to the cell membrane, triggering the rupture of the cell membrane, and the cell contents discharge, leading to the occurrence of non-canonical pyroptosis. After activation of caspase-11, it also promotes the canonical pyroptosis, activates and releases interleukin-1β and interleukin-18, which aggravated inflammation. Caspase-4/5/11, GSDM-D, Toll-like receptor 4 and high mobility group protein B1 are the key molecules of the non-canonical pyroptosis. Exploring the mechanisms of non-canonical pyroptosis and the related research progresses in inflammatory diseases intensively is of great significance for clinical prevention and treatment of the relevant diseases.
Caspases ; Humans ; Inflammasomes ; Inflammation ; Lipopolysaccharides ; Pyroptosis ; Sepsis

Epilepsy is one of the most common episodic neurological diseases characterized by recurrent epileptic seizures. The seizures occur by synchronization of a neuronal network, which may cause disturbances in intracellular ion homeostasis, neuronal excitability, network remodeling, and neuronal death. The neuronal death following epileptic seizures results from the execution of cellular programs that are similar to those in developmentally programmed cell death. Research into cell death after seizures has identified the molecular machinery of apoptosis including the caspases and bcl-2 family proteins. The author reviews the clinical experimental evidences of programmed death pathway function in epileptic seizures. Four neuronal death pathways after epileptic seizures are proposed; non-programmed necrotic, programmed necrotic, programmed apoptotic extrinsic, and programmed apoptotic intrinsic pathways. Epileptogenesis is speculated based on the programmed pathways. Research on seizure-induced neuronal damage has developed considerably in recent years and that may open new ways to improve neuroprotective and antiepileptic treatments for patients with epilepsy.
Apoptosis ; Caspases ; Cell Death* ; Epilepsy* ; Homeostasis ; Humans ; Neurons ; Seizures

Caspases ; genetics ; Genetic Predisposition to Disease ; Humans ; Neoplasms ; genetics ; Polymorphism, Genetic

Chemical investigation of the culture extract of an endophytic Penicillium citrinum from Dendrobium officinale, afforded nine citrinin derivatives (1-9) and one peptide-polyketide hybrid GKK1032B (10). The structures of these compounds were determined by spectroscopic methods. The absolute configurations of 1 and 2 were determined for the first time by calculation of electronic circular dichroism (ECD) data. Among them, GKK1032B (10) showed significant cytotoxicity against human osteosarcoma cell line MG63 with an IC₅₀ value of 3.49 μmol·L^-1, and a primary mechanistic study revealed that it induced the apoptosis of MG63 cellsvia caspase pathway activation.
Apoptosis ; Bone Neoplasms ; Caspases ; Humans ; Osteosarcoma/drug therapy* ; Penicillium

Nitric oxide (NO) is a short-lived gaseous free radical that predominantly functions as a messenger and effector molecule. It affects a variety of physiological processes, including programmed cell death (PCD) through cyclic guanosine monophosphate (cGMP)-dependent and - independent pathways. In this field, dominant discoveries are the diverse apoptosis networks in mammalian cells, which involve signals primarily via death receptors (extrinsic pathway) or the mitochondria (intrinsic pathway) that recruit caspases as effector molecules. In plants, PCD shares some similarities with animal cells, but NO is involved in PCD induction via interacting with pathways of phytohormones. NO has both promoting and suppressing effects on cell death, depending on a variety of factors, such as cell type, cellular redox status, and the flux and dose of local NO. In this article, we focus on how NO regulates the apoptotic signal cascade through protein S-nitrosylation and review the recent progress on mechanisms of PCD in both mammalian and plant cells.
Animals ; Apoptosis ; physiology ; Caspases ; metabolism ; Caspases, Effector ; metabolism ; Cyclic GMP ; metabolism ; Mitochondria ; metabolism ; physiology ; Nitric Oxide ; metabolism ; physiology ; Plant Cells ; Plant Physiological Phenomena ; Signal Transduction ; physiology

The aim of study was to investigate the effect of a traditional Chinese medicine, emodin, on proliferation and apoptosis in T lymphocytic leukemic cell line Jurkat and its mechanisms. Cell proliferation inhibition was detected by MTT assay. Cell apoptosis was measured by DNA ladder and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay. The expressions of related proteins and caspase family members were determined by Western blot. The results showed that emodin inhibited proliferation in Jurkat cells, with an IC50 about 20 micromol/L and induced cell apoptosis in both time-and dose-dependent manners. The expressions of proliferation-related protein C-MYC, hTERT and apoptosis-related protein BCL-2 were down-regulated in a time dependent manner after the treatment with emodin. The expressions of procaspase-3, -8 and -9 all decreased while activated caspase-3 and PARP expressions were up-regulated. It is concluded that emodin can remarkably inhibit cell proliferation and induce apoptosis in Jurkat cells. The down-regulation of proliferation-related proteins C-MYC, hTERT and apoptosis-related protein BCL-2 expressions and activation of caspase cascade may be involved in the process of apoptosis.
Apoptosis ; drug effects ; Caspases ; metabolism ; Cell Proliferation ; drug effects ; Emodin ; metabolism ; pharmacology ; Humans ; Jurkat Cells

OBJECTIVETo study the effect of valproate acid sodium(VPA) on apoptosis of human gastric cancer cell BGC-823 and to explore its possible mechanism.

METHODSCell growth inhibition was examined by MTT assay. Apoptosis rate was detected by FCM with Annexin V/PI staining. The activities and protein expression levels of caspase 3, caspase 8 and caspase 9 were examined by spectrophotometry and indirect immunofluorescence technique respectively.

RESULTSThe growth inhibition rate and apoptosis rate of human gastric cancer cells, treated with 0.75-4.00 mmol/L VPA for 24 h and 48 h, elevated in time- and dose-dependent manner. Apoptosis rates of VPA 0.75 mmol/L 24 h and 48 h were (7.2 +/- 0.5)% and (9.2 +/- 1.0)%, of VPA 4.00 mmol/L 24 h and 48 h were (16.7 +/- 2.2)% and (20.4 +/- 1.6)% respectively, which were significantly different as compared to the control [24 h, (4.9 +/- 0.2)%, 48 h, (5.1 +/- 0.8)%] (P< 0.001). The activities and protein expression levels of caspase 3 and caspase 9 were up-regulated compared with the control group (P< 0.001), meanwhile the activity and protein expression of caspase 8 enhanced slightly after VPA treatment for 48 h.

CONCLUSIONVPA can inhibit the growth and induce the apoptosis of BGC-823 cells mainly through the activation of caspase 9 pathway.

Apoptosis ; drug effects ; Caspases ; metabolism ; Cell Line, Tumor ; Humans ; Stomach Neoplasms ; pathology ; Valproic Acid ; pharmacology

BACKGROUND: Defects in mitochondrial function have been shown to participate in the induction of neuronal cell injury. The extracellular-signal-regulated kinase (ERK) signaling pathway plays a crucial role in almost all cell functions, including proliferation, differentiation, survival, and death. However, the effect of ERK inhibition on oxysterol-induced apoptosis remains uncertain. METHODS: This study assessed the effect of ERK inhibition on the apoptotic effect of 7-ketocholesterol. RESULTS: Treatment with 7-ketocholesterol increased phosphorylated-ERK1/2 levels in differentiated PC12 cells, while the total amount of ERK was not altered. 7-Ketocholesterol decreased Bid and Bcl-2 levels, increased Bax and p53 levels, and promoted cytochrome c release, which elicits the activation of caspases (-8, -9, and -3), nuclear damage, and cell death. ERK and farnesyltransferase inhibitors inhibited the 7-ketocholesterol-induced phosphorylation of ERK1/2, activation of apoptosis-related proteins, and cell death in PC12 cells. CONCLUSIONS: The ERK and farnesyltransferase inhibitors, which did not exhibit toxicity, may inhibit the 7-ketocholesterol toxicity on differentiated PC12 cells by suppressing the activation of the caspase-8-dependent pathway as well as activation of the mitochondria-mediated cell-death pathway, leading to the activation of caspases. The inhibition of ERK may confer a beneficial protective effect against the neuronal cell injury induced by cholesterol oxidation products.
Animals ; Apoptosis ; Caspases ; Cell Death ; Cholesterol ; Cytochromes c ; Farnesyltranstransferase ; Ketocholesterols ; Neurons ; PC12 Cells ; Phosphorylation ; Phosphotransferases ; Proteins

BACKGROUND: Human telomerase is a ribonucleoprotein polymerase, which synthesizes telomeric repeat sequences, and human telomerase reverse transcriptase (hTERT) has been identified as the catalytic subunit, as well as the rate-limiting component, of telomerase. In this study, we attempted to identify the modulators of telomerase, and to determine the molecular mechanisms underlying cisplatin-induced apoptosis. METHODS: To determine the role of telomerase in cisplatin-induced apoptosis, we measured telomerase activity and analyzed apoptosis using PI and trypan blue staining. Also, we inhibited the caspase activations using Z-VAD-fmk to analyze the effects on expression of hTERT protein. Finally, we induced the transient co-expression of the Bcl-2 and Bak genes in HEK293 cells, and then, the telomerase activity and expression of hTERT were evaluated. RESULTS: In the Bcl-2-overexpressing HeLa cells, telomerase activity was more enhanced, and cell death was reduced to 40-50% that of the mock controls. This finding suggests that Bcl-2-induced telomerase activity exerts an antiapoptotic effect in cisplatin-induced death. As caspase activation was inhibited via Z-VAD-fmk, the hTERT protein was recovered in the mock controls, but not in the Bcl-2-overexpressing cells. This suggests that the expression of hTERT can be regulated by caspases, but Bcl-2 was located within the upstream pathway. Moreover, when the Bcl-2 and Bak genes were co-transfected into the HEK293, both telomerase activity and hTERT protein were prominently reduced. CONCLUSIONS: Bcl-2-induced telomerase activity inhibits cisplatin-induced apoptosis in HeLa cells, and can be regulated via both caspases and the interaction of Bcl-2 and Bak.
Apoptosis ; Caspases* ; Catalytic Domain ; Cell Death* ; Cisplatin ; HEK293 Cells ; HeLa Cells ; Humans* ; Ribonucleoproteins ; Telomerase* ; Trypan Blue

PURPOSE: The potential therapeutic application of the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), in the treatment of multiple myeloma (MM), was recently proposed. However, there have been some problems with the use of TRAIL, due to the appearance of TRAIL-resistant cells in MM. The effect of arsenic trioxide (As2O3) on the rate of apoptosis induced by TRAIL was evaluated in MM cells. MATERIALS AND METHODS: Using TRAIL-sensitive (RPMI- 8226) and TRAIL-resistant (ARH-77 and IM-9) MM cell lines, the cell viability, induction of apoptosis, and change in the caspases were examined after treatment with TRAIL alone, or in combination with various concentrations of As2O3. RESULTS: Incubating the cell lines with As2O3 augmented the TRAIL-induced apoptosis in the MM cell lines, according to the As2O3 concentration. Apoptosis was mediated through caspase activation. When TRAIL was used alone, caspase8 was activated in the RPMI-8226 cell lines, but not in the ARH-77 and IM-9 cell lines. When As2O3 was added to TRAIL, caspase-9 was activated in the ARH-77 and IM-9 cells. CONCLUSION: The use of As2O3, in combination with TRAIL, would help enhance the level of TRAIL-induced apoptosis, and overcome the TRAIL-resistance, in MM cells.
Apoptosis* ; Arsenic* ; Caspase 9 ; Caspases ; Cell Line* ; Cell Survival ; Multiple Myeloma* ; Necrosis*