Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P42574 (caspase-3)
 45,978 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Protocatechuic acid (PCA), a phenolic compound isolated from the kernels of Alpinia oxyphylla, showed anti-oxidant neuroprotective property in our previous study. However, it is still unknown whether PCA have effects on the cultured neural stem cells (NSCs). In this study, we investigated the roles of PCA in the survival and apoptosis of rat NSCs under normal conditions. NSCs obtained from 13.5-day-old rat embryos were propagated as neurospheres and cultured under normal conditions with or without PCA for 4 and 7 days. The cell viability was determined by the cell counting kit-8 (CCK-8) test, while cell proliferation was assayed by bromodeoxyuridine (BrdU) labeling. PCA increased the cellular viability of NSCs and stimulated cell proliferation in a dose- and time-dependent manner. Apoptotic cells were detected after 4 days by observing the nuclear morphological changes and flow cytometric analysis. Compared with the control on both culture days, treatment with PCA effectively reduced the levels of apoptosis of NSCs. At the same time, the reactive oxygen species (ROS) level in NSCs was depressed. In addition, PCA also significantly decreased the activity of elevated caspase-3, indicating that PCA may inhibit apoptosis of NSCs via suppression of the caspase cascade. These results suggest that PCA may be a potential growth inducer and apoptosis inhibitor for NSCs.
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PMID:Protocatechuic acid promotes cell proliferation and reduces basal apoptosis in cultured neural stem cells. 1909 56

Diabetic retinopathy (DR) is a leading cause of vision loss among working-age adults. Retinal endothelial cell apoptosis is an early event in DR, and oxidative stress is known to play an important role in this pathology. Recently, we found that high glucose induces apoptosis in retinal neural cells by a caspase-independent mechanism. Here, we investigated the mechanisms underlying retinal endothelial cell apoptosis induced by high glucose and oxidative/nitrosative stress conditions. Endothelial cells (TR-iBRB2 rat retinal endothelial cell line) were exposed to high glucose (long-term exposure, 7 days), or to NOC-18 (nitric oxide donor; 250microM) or H(2)O(2) (100microM) for 24h. Cell viability was assessed by the MTT assay and cell proliferation by [methyl-(3)H]-thymidine incorporation into DNA. Apoptotic cells were detected with Hoechst or Annexin V staining. Active caspases were detected by an apoptosis detection kit. Active caspase-3 and apoptosis-inducing factor (AIF) protein levels were assessed by Western blot or immunohistochemistry. High glucose, NOC-18 and H(2)O(2) increased apoptosis in retinal endothelial cells. High glucose and mannitol decreased cell proliferation, but mannitol did not induce apoptosis. Caspase activation did not increase in high glucose- or NOC-18-treated cells, but it increased in cells exposed to H(2)O(2). However, the protein levels of AIF decreased in mitochondrial fractions and increased in nuclear fractions, in all conditions. These results are the first demonstrating that retinal endothelial cell apoptosis induced by high glucose is independent of caspase activation, and is correlated with AIF translocation to the nucleus. NOC-18 and H(2)O(2) also activate a caspase-independent apoptotic pathway, although H(2)O(2) can also induce caspase-mediated apoptosis.
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PMID:High glucose and oxidative/nitrosative stress conditions induce apoptosis in retinal endothelial cells by a caspase-independent pathway. 1914 53

Chronic lymphocytic leukemia (CLL) cells are characterized by defective apoptosis which leads to their extended survival. Arsenic trioxide (As(2)O(3)) was reported to induce cell death in many malignant cells, but the specific pathway of As(2)O(3)-induced apoptosis/necrosis remains controversial. Our aim was to determine if As(2)O(3) kills CLL cells through apoptosis and whether this is accompanied by reduction in Bcl-2 levels. Cells from nine patients with CLL were incubated with increasing concentrations of As(2)O(3) (0.5-2 microM) for 2, 7, or 14 days. Cells viability was measured using Alamar Blue assay and apoptosis using human Annexin V-FITC and propidium iodine (PI) kit (BMS306FI; Bender MedSystems, Vienna, Austria). Intracellular Bcl-2, Bax, and caspase-3 levels were measured by flow cytometry. As(2)O(3) significantly reduced CLL cell viability (P < 0.01) and induced apoptotic cell death in a time- and dose-dependent manner. After 7 days, CLL cells showed a significant decrease in mean fluorescence intensity (MFI) of Bcl-2 on flow cytometry study. Bax and caspase-3 levels showed significant decrease in MFI only after prolonged incubations (7 and 14 days) and mostly at higher concentrations of As(2)O(3). The mechanism underlying the reduction in viability of CLL cells incubated with As(2)O(3) is mediated by induction of apoptosis maybe through the down-regulation of Bcl-2. Further studies are needed to elucidate the potential therapeutic role of As(2)O(3) in CLL.
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PMID:Arsenic-trioxide-induced apoptosis of chronic lymphocytic leukemia cells. 1920 92

We have previously found that adhesion fibroblasts exhibit lower apoptosis and higher protein nitration as compared with normal peritoneal fibroblasts. In this study, we sought to determine whether the decreased apoptosis observed in adhesion fibroblasts is caused by lower caspase-3 activity due to an increase in caspase-3 S-nitrosylation. For this study, we have utilized primary cultures of fibroblasts obtained from normal peritoneum and adhesion tissues of the same patient(s). Cells were treated with increasing concentrations of peroxynitrite and cell lysates were immunoprecipitated with anti-caspase-3 polyclonal antibody. The biotinylated proteins were detected using a nitrosylation detection kit. Caspase-3 activity and apoptosis were measured by colorimetric and TUNEL assays, respectively. Our results showed that caspase-3 S-nitrosylation is significantly higher in adhesion fibroblasts as compared with normal peritoneal fibroblasts. This increase in S-nitrosylation resulted in a 30% decrease in caspase-3 activity in adhesion fibroblasts. Peroxynitrite treatment resulted in a dose response increase in caspase-3 S-nitrosylation, leading to a decrease in caspase-3 activity and apoptosis in normal peritoneal fibroblasts. We conclude that S-nitrosylation of caspase-3 is the reason for its decreased activity and subsequent decrease in apoptosis of adhesion fibroblasts. The mechanism by which caspase-3 S-nitrosylation occurs is not fully understood. However, the role of hypoxia in the formation of peroxynitrite via superoxide production may suggest a possible mechanism.
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PMID:S-nitrosylation of caspase-3 is the mechanism by which adhesion fibroblasts manifest lower apoptosis. 1932 Aug 91

Renin-angiotensin system (RAS) plays a central role in the development and progression of diabetic nephropathy. Further, there is a growing body of evidence that advanced glycation end products (AGEs) and their receptor (RAGE) axis also contributes to diabetic nephropathy. However, the pathophysiological crosstalk between the RAS and AGE-RAGE system in tubular cell injury, which is more important than glomerulopathy in terms of renal prognosis in diabetic nephropathy, remains unknown. In this study, we examined whether and how irbesartan, an angiotensin II type 1 receptor blocker (ARB), inhibited the AGE-induced tubular cell apotptosis and damage in vitro. Gene expression was analyzed by quantitative real-time reverse transcription-polymerase chain reactions. Intracellular formation of reactive oxygen species (ROS) was measured with dihydroethidium staining. Apoptosis levels were evaluated for DNA fragments with an enzyme-linked immunosorbent assay kit and for caspase-3 activity. Irbesartan inhibited the AGE-induced up-regulation of RAGE mRNA levels and subsequently reduced ROS generation in human proximal tubular cells. AGEs induced apoptosis and increased inflammatory, thrombogenic and fibrogenic gene expressions in tubular cells, which were also blocked by the treatment with irbesartan. Our present data suggest that there exists a crosstalk between the RAS and AGE-RAGE system in tubular cell apoptosis and damage. Blockade of the RAS by irbesartan may play a protective role against tubular injury in diabetes by attenuating the deleterious effects of AGEs via down-regulation of RAGE.
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PMID:Irbesartan inhibits advanced glycation end product (AGE)-induced proximal tubular cell injury in vitro by suppressing receptor for AGEs (RAGE) expression. 1963 64

Canine osteosarcoma, an aggressive cancer with early distant metastasis, shows still despite good chemotherapy protocols poor long term survival. The aim of our study was to determine whether sorafenib, a novel multikinase inhibitor, has any effect on D-17 canine osteosarcoma cells. A cell proliferation kit was used for detecting surviving cells after treatment for 72 h with sorafenib or carboplatin or their combination. A significant decrease of neoplastic cells was observed after incubation with 0.5-16 microM sorafenib or with 80-640 microM carboplatin. Using immunocytochemistry for activated caspase 3 to evaluate apoptosis, we found significantly more positive cells in the sorafenib treated groups. Paradoxically, expression of the nuclear proliferation marker Ki-67 was also significantly higher in sorafenib treated cells. The drug sorafenib showed potent antitumour activity against D-17 canine osteosarcoma cells in vitro, suggesting a potential as a therapeutic tool in the treatment of bone cancer in dogs.
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PMID:The tyrosine kinase inhibitor sorafenib decreases cell number and induces apoptosis in a canine osteosarcoma cell line. 1966 56

This study investigates the simultaneous effect of acrylamide (ACR) and high-fat-intake on the apoptosis in testis cells, and also the expression and activity of caspase-3. Seventy-two male Kunming mice were divided into two blocks and fed with a high-fat diet (crude fat 21.5%) or basic diet (crude fat 4.4%), respectively; and animals in each diet block were exposed to ACR at the dose of 20 mg/kgbw x d or 40 mg/kgbw x d as ACR treated groups or the normal saline as control. Germ cells prepared from testis were stained with Hoechst dye 33258 and paraffin wax sections from testis were suffered to a TUNEL process. Expression of caspase-3 on protein level was investigated using an immunohistochemical analysis assay. The supernatant of unilateral testes were subjected to a Caspase-3 activity kit to determine the activity of Caspase-3 in testis. The concentration of ACR and glycidamide(GA), epoxide of ACR, in plasma and testis were detected by LC-ES/MS/MS analysis. Results based on the morphological changes, percentage of apoptotic cells, and integrated optical density (IOD) of positive amethyst staining which indicates the apoptotic DNA fragmentation, show that apoptosis was induced by acrylamide only; however, acrylamide-induced apoptosis was weakened by high-fat-intake. The protein expression and activity of Caspase-3 were not induced by ACR or high-fat-intake. Moreover, no significant differences of ACR and GA concentration were found between the high-fat and basic diet groups after exposure of ACR. Results indicate that high-fat-intake reverses the effects on apoptosis induced by ACR; and more possibly, apoptosis is induced by a caspase-3-independent mechanism.
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PMID:Apoptosis induced by acrylamide is suppressed in a 21.5% fat diet through caspase-3-independent pathway in mice testis. 1975 22

L-3,4-Dihydroxyphenylalanine (L-DOPA) is one of the most important drugs for the treatment of Parkinson's disease (PD). Although neurotoxicity of L-DOPA remains controversial, there are many reports suggesting that L-DOPA causes neuronal death. We investigated whether the neurotoxic effect of L-DOPA could be inhibited by the activation of the phosphatidylinositol 3-kinase (PI3K) pathway. Cell counting kit-8, trypan blue staining, and DAPI staining all showed that L-DOPA decreased nPC12 cell viability at high concentrations. However, combined treatment with the PI3K activator and L-DOPA significantly increased the viability of nPC12 cells when compared with treatment with L-DOPA only. Phosphorylated Akt (Ser473), phosphorylated glycogen synthase kinase-3beta (GSK-3beta) (Ser9), and heat shock transcription factor-1, which are survival-related signaling proteins, were decreased in nPC12 cells treated with 200 microM L-DOPA, but were significantly increased with combined treatment with the PI3K activator in a concentration-dependent manner. However, treatment of L-DOPA significantly increased expressions of cytosolic cytochrome c and cleaved caspase-3, which are death-related signaling proteins, in nPC12 cells, but combined treatment with the PI3K activator reduced those expressions. To confirm whether the effect of the PI3K activator is associated with direct activation of PI3K, LY294002, a PI3K inhibitor, was used to pretreat the nPC12 cells prior to combined treatment with the PI3K activator and L-DOPA. The protective effect of the PI3K activator was almost completely blocked. Together, these results suggest that L-DOPA neurotoxicity can be prevented by PI3K activation.
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PMID:L-DOPA-induced neurotoxicity is reduced by the activation of the PI3K signaling pathway. 1978 63

This study was aimed to investigate the apoptosis-inducing effect of gambogic acid (GA) on K562 cell line and its mechanism. The K562 cells were treated with GA at different concentrations and times, the inhibition rates were detected by MTT assay. Apoptosis induced by GA was assayed by Annexin-V/PI doubling staining. The influence of GA on cell cycle was studied by propidium iodide method. The mitochondrial membrane potential was measured by JC assay. The levels of caspase 3, caspase 8 and caspase 9 activated by fluorescein in living K562 cells were measured by caspGLOW(TM) fluorescein staining kit. The results showed that after incubation with GA, K562 cell proliferation was dramatically inhibited in concentration- and time-dependent manners. K562/A02 cells need higher GA concentration (> 2 microg/ml) to show antiproliferative effect, compared with that of K562 cells (> 0.5 microg/ml). Apoptosis could be induced by GA but the influence on cell cycle was not significant. GA could decrease the mitochondrial membrane potential and increase the activated caspase 3, caspase 8, caspase 9 positive cell levels by 2.19%, -1.95%, 34.01% in 24 hr and 60.4%, 71.3%, 77.7% in 48 hr respectively. It is concluded that the GA can significantly inhibit the proliferation of K562 cells without influence on cell cycles. The GA triggers K562 cell apoptosis through both intrinsic and extrinsic pathways.
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PMID:[Apoptosis-inducing effect of gambogic acid on K562 cells and its mechanism]. 2003 Sep 23

This study aims to investigate the inhibitory effect on proliferation and metastasis of 20-O-(beta-D-glucopyranosyl)-20(S)-protopanaxadiol (IH901) on ECV304 cell line. MTT assay was used to examine the effect of cell proliferation inhibition and the adhesive ability of ECV304 cells to artificial basement membrane. Morphology of cell apoptosis was observed with phase contrast microscope. Apoptosis rate and cell cycle were detected by flow cytometry (FCM). Cell migration was measured by wound healing assay. ELISA kit was used to detect VEGF and bFGF. Caspases were detected by Western blotting. Results indicated that ginseng saponin IH901 can downregulate the expression of growth promoting protein VEGF and bFGF, and upregulate pro apoptosis protein cleaved caspase-9 and cleaved caspase-3. The increase in the apoptotic sub-G1 fraction is in a dose-dependent manner, and cell cycle arrests in the G0/G1 phase was detected by FCM. Morphological examination of IH901-treated samples showed cells with chromatin condensation, cell shrinkage, and all typical characteristics of apoptotic cells. Therefore, IH901 dramatically suppresses cell proliferation and adhesion and migration of ECV304 cell line.
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PMID:[Inhibitory effect of ginseng saponin IH901 on proliferation and metastasis of ECV304 cell line and its molecular mechanism]. 2005 70


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