Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P10415 (Bcl-2)
 33,771 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acceleration of blood leukocyte apoptosis in major depression has been described. The present studies have been undertaken to estimate the level of apoptosis of blood leukocytes in patients with depression and to examine the mechanisms leading to apoptosis. Blood was taken from 29 patients with depression (age 48.2+/-11.2, 14 males, 15 females) and 30 healthy controls (age 41.3+/-4.1, 15 males, 15 females), and apoptosis was estimated by the cytometric method by measurements of annexin V binding, mitochondrial membrane potential (DeltaPsi), bcl-2, bax, and Fas (CD95) expression in CD4+, CD8+ and CD14+ cells. The amounts of cytochrome c released from mitochondria to cytosol of peripheral blood mononuclear cells (PBMCs) and polymorphonuclear cells (PMNs) were also measured. The levels of reactive oxygen species (ROS) released from PMNs were examined as was the serum activity of superoxide dismutase (SOD), catalase (CAT), and total peroxidase (PER). Additionally, serum levels of the tumor necrosis factor (TNF-alpha) and interleukin-6 (IL-6) were estimated. Our experiments indicated accelerated apoptosis of CD4+ T lymphocytes and CD14+ cells (mainly neutrophils) of depressed patients as well as a significant increase in the percent of Fas-expressing cells. Bcl-2 and bax expression was higher in cells of depressed patients than in control, however, bcl-2/bax ratio was significantly decreased in CD14+ cells of depressed patients. PMNs isolated from the blood of the patients produced more ROS spontaneously and after induction with phorbol ester (PMA) than PMNs of the healthy control. A significant increase in serum activity of SOD, CAT and PER was also detected. Overproduction of superoxide anion correlated positively with the level of PMNs apoptosis (measured by cytochrome c release), suggesting that superoxide anion might be an important factor inducing apoptotic death of blood cells. The result of our experiment indicated that apoptosis of immune cells may affect patient's susceptibility to different infections and application of antioxidants in medication of patients with depression will be beneficial for them. The increased level of IL-6 in sera of the depressed patients did not correlate with overproduction of ROS, suggesting that this cytokine is not involved in oxidative stress and apoptosis of leukocytes.
 ...
PMID:Accelerated apoptosis of blood leukocytes and oxidative stress in blood of patients with major depression. 1808 80

This study investigated the proapoptotic effects of oxidized low density lipoprotein (oxLDL), which plays a key role in atherogenesis, on normal fresh human monocytes isolated from peripheral blood (PBMs), on human monocyte-derived macrophages, and on U937 monocytic cell line. OxLDL were generated by hypochlorous acid (HOCl) treatment of native LDL. We demonstrated that HOCl-oxLDL (200 microg/ml) induced apoptosis in PBMs and U937 cells via the mitochondrial pathway, whereas it failed to induce apoptosis in human monocyte-derived macrophages. OxLDL-induced U937 cells apoptosis involved ROS generation, mitochondrial Bax translocation with a disruption of mitochondrial membrane potential, cytosolic liberation of cytochrome c and subsequently activation of caspases-9 and -3. The interference of ROS scavengers N-acetylcysteine and catalase with HOCl-oxLDL-induced apoptosis further supports the importance of mitochondrial ROS production in this process. Bcl-2 overexpression prevented Bax translocation whereas it failed to prevent ROS generation indicating that ROS is an upstream signal for inducing mitochondrial apoptotic damages. Because monocyte apoptosis could limit early atheroma formation, it will be interesting to identify the signaling pathway(s) induced by HOCl-oxLDL leading to ROS generation. In contrast, monocyte-derived macrophages, which resist to HOCl-oxLDL-induced oxidative stress, may promote atherosclerosis.
 ...
PMID:Role of reactive oxygen species and Bax in oxidized low density lipoprotein-induced apoptosis of human monocytes. 1828 75

Steroid hormones have been reported to activate various signal transducers that trigger a variety of cellular responses. Among these hormones, testosterone has been identified as an antioxidant that protects against cellular damage. Therefore, using mouse embryonic stem (ES) cells as a model system, this study evaluated the effects of dihydrotestosterone (DHT), a biologically active testosterone metabolite, on H2O2-induced apoptosis. H2O2 increased the release of lactate dehydrogenase (LDH) and DNA fragmentation but reduced the cell viability in a time-dependent manner (> or =8 h). Moreover, H2O2 decreased the level of DNA synthesis and the levels of the cell cycle regulatory proteins [cyclin D1, cyclin E, cyclin-dependent kinase (CDK) 2, and CDK 4]. These effects of H2O2 were inhibited by a pretreatment with DHT. However, a treatment with flutamide (androgen receptor inhibitor, 10(-3) M) abolished the protective effects of DHT. This result was supported by the presence of the androgen receptor in mouse ES cells. The activity of the antioxidant enzyme, catalase, was increased by the DHT treatment but not by a co-treatment with DHT and flutamide. Using CM-H(2)DCFDA (DCF-DA) for the detection of intracellular H2O2, DHT decreased the intracellular H2O2 levels but flutamide blocked this effect. H2O2 also increased the level of p38 MAPK, JNK/SAPK, and NF-kappaB phosphorylation, which were inhibited by the DHT pretreatment. Catalase inhibited the effect of H2O2 on MAPKs and NF-kappaB. However, the flutamide treatment abolished the inhibitory effects of DHT on the H2O2-induced increase in the levels of p38 MAPK, JNK/SAPK, and NF-kappaB phosphorylation. DHT inhibited the H2O2-induced increase in caspase-3 expression and decreased the level of Bcl-2 and the cellular inhibitor of apoptosis protein (cIAP)-2. These effects were abolished by the flutamide treatment. In conclusion, DHT prevents the H2O2-induced apoptotic cell death of mouse ES cells through the activation of catalase and the downregulation of p38 MAPK, JNK/SAPK, and NF-kappaB via the androgen receptor.
 ...
PMID:Effect of dihydrotestosterone on hydrogen peroxide-induced apoptosis of mouse embryonic stem cells. 1833 Aug 93

Curcumin, a well-known dietary pigment derived from Curcuma longa, inhibited growth of several types of malignant cells both in vivo and in vitro. Its effects on cell proliferation and the induction of apoptosis in human bladder cancer cell lines and intravesical activity in a rat bladder tumor model were studied. Exposure of human bladder cancer cells to curcumin resulted in the induction of apoptotic cell death and caused cells to arrest in the G2/M phase. The anti-apoptotic Bcl-2 and Survivin protein was downregulated by the curcumin treatment together with enhancement of the Bax and p53 expression. The inhibitory activities of curcumin were stronger than those of cisplatin and could not be prevented by catalase pretreatment in T24 cells. Clonal assay indicated large-dose and short-term curcumin was lethal to bladder cancer cells. Moreover, the in vivo study revealed curcumin did induce apoptosis in situ, inhibit and slow the development of bladder cancer. These observations suggest that curcumin could prove an effective chemopreventive and chemotherapy agent for bladder cancer.
 ...
PMID:Effects of curcumin on bladder cancer cells and development of urothelial tumors in a rat bladder carcinogenesis model. 1834 36

Apigenin, a plant flavone, potentially activates wild-type p53 and induces apoptosis in cancer cells. We conducted detailed studies to understand its mechanism of action. Exposure of human prostate cancer 22Rv1 cells, harboring wild-type p53, to growth-suppressive concentrations (10-80 microM) of apigenin resulted in the stabilization of p53 by phosphorylation on critical serine sites, p14ARF-mediated downregulation of MDM2 protein, inhibition of NF-kappaB/p65 transcriptional activity, and induction of p21/WAF-1 in a dose- and time-dependent manner. Apigenin at these doses resulted in ROS generation, which was accompanied by rapid glutathione depletion, disruption of mitochondrial membrane potential, cytosolic release of cytochrome c, and apoptosis. Interestingly, we observed accumulation of a p53 fraction to the mitochondria, which was rapid and occurred between 1 and 3 h after apigenin treatment. All these effects were significantly blocked by pretreatment of cells with the antioxidant N-acetylcysteine, p53 inhibitor pifithrin-alpha, and enzyme catalase. Apigenin-mediated p53 activation and apoptosis were further attenuated by p53 antisense oligonucleotide treatment. Exposure of cells to apigenin led to a decrease in the levels of Bcl-XL and Bcl-2 and increase in Bax, triggering caspase activation. Treatment with the caspase inhibitors Z-VAD-FMK and DEVD-CHO partially rescued these cells from apigenin-induced apoptosis. In vivo, apigenin administration demonstrated p53-mediated induction of apoptosis in 22Rv1 tumors. These results indicate that apigenin-induced apoptosis in 22Rv1 cells is initiated by a ROS-dependent disruption of the mitochondrial membrane potential through transcriptional-dependent and -independent p53 pathways.
 ...
PMID:Apigenin-induced prostate cancer cell death is initiated by reactive oxygen species and p53 activation. 1834 37

Maternal diabetes affects the development of the offspring by altering the uterine environment. We aimed to investigate the extent to which the blood flow (measured as Tissue Perfusion Units; TPU) to implantation sites and the expression of developmentally important genes in the offspring are affected by maternal diabetes. We measured mRNA levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), Bcl-2 associated X protein (Bax), B-cell lymphoma protein (Bcl-2), tumor suppressor protein-53 (p53), paired box protein-3 (Pax-3) and vascular endothelial growth factor-A (Vegf-A). Moreover, we studied the effect on uterine blood flow (TPU) and the expression of the genes exerted by embryonic maldevelopment (malformation or resorption). Streptozotocin induced diabetic (D) and non-diabetic (N) pregnant rats were used in the study. Blood flow (TPU) to implantation sites was measured by a laser Doppler flow meter, and gene expression was analyzed by RT-PCR. Maternal diabetes caused increased blood flow (TPU) to implantation sites compared with normal pregnancy. Furthermore, implantation sites of D rats containing malformed offspring showed impaired growth and decreased blood flow (TPU) compared with their littermates at all gestational days. Resorbed offspring from both N and D rats displayed increased blood flow (TPU) compared with their non-resorbed littermates. Moreover, we found that maternal diabetes causes decreased expression of genes involved in the oxidative stress defense system (CuZnSOD in non-malformed D11 embryos, MnSOD at all gestational time points, ECSOD and Gpx-1 at GD11-GD15, CAT and Gpx-2 at GD15), decreased expression of Pax-3 at GD11, and increased expression of Vegf-A at all gestational time points. We conclude that both maternal metabolism and embryonic developmental state affect the blood flow (TPU) to the implantation site. Maternal diabetes causes decreased expression of anti-oxidative enzymes and enhanced angiogenesis in the offspring in rats.
 ...
PMID:Altered uterine perfusion is involved in fetal outcome of diabetic rats. 1838 70

Extensive research within the last decade has revealed that most chronic illnesses such as cancer, cardiovascular and pulmonary diseases, neurological diseases, diabetes, and autoimmune diseases exhibit dysregulation of multiple cell signaling pathways that have been linked to inflammation. Thus mono-targeted therapies developed for the last two decades for these diseases have proven to be unsafe, ineffective and expensive. Although fruits and vegetables are regarded to have therapeutic potential against chronic illnesses, neither their active component nor the mechanism of action is well understood. Resveratrol (trans-3, 5, 4'-trihydroxystilbene), a component of grapes, berries, peanuts and other traditional medicines, is one such polyphenol that has been shown to mediate its effects through modulation of many different pathways. This stilbene has been shown to bind to numerous cell-signaling molecules such as multi drug resistance protein, topoisomerase II, aromatase, DNA polymerase, estrogen receptors, tubulin and F1-ATPase. Resveratrol has also been shown to activate various transcription factor (e.g; NFkappaB, STAT3, HIF-1alpha, beta-catenin and PPAR-gamma), suppress the expression of antiapoptotic gene products (e.g; Bcl-2, Bcl-X(L), XIAP and survivin), inhibit protein kinases (e.g; src, PI3K, JNK, and AKT), induce antioxidant enzymes (e,g; catalase, superoxide dismutase and hemoxygenase-1), suppress the expression of inflammatory biomarkers (e.g., TNF, COX-2, iNOS, and CRP), inhibit the expression of angiogenic and metastatic gene products (e.g., MMPs, VEGF, cathepsin D, and ICAM-1), and modulate cell cycle regulatory genes (e.g., p53, Rb, PTEN, cyclins and CDKs). Numerous animal studies have demonstrated that this polyphenol holds promise against numerous age-associated diseases including cancer, diabetes, Alzheimer, cardiovascular and pulmonary diseases. In view of these studies, resveratrol's prospects for use in the clinics are rapidly accelerating. Efforts are also underway to improve its activity in vivo through structural modification and reformulation. Our review describes various targets of resveratrol and their therapeutic potential.
 ...
PMID:Resveratrol: a multitargeted agent for age-associated chronic diseases. 1841 53

Our previous studies have shown that bee venom (BV) can induce apoptosis in human cervical cancer Ca Ski cells, but it can also affect human breast cancer cells, though its molecular mechanisms are not precisely known. In this study, the molecular mechanisms of apoptosis induced by BV in human breast cancer MCF7 cells were investigated. BV induced morphological changes (examined by phase-contrast microscopy) and inhibited the proliferation (examined by MTT assay) of MCF7 cells; both effects occurred in a dose- and time-dependent manner. Flow cytometric analysis demonstrated that BV induced the production of reactive oxygen species (ROS) and dysfunction of the mitochondrial membrane potential (Azm), and led to cytochrome c release, an increase in the levels of caspase-9 and Poly (ADP-ribose) polymerase (PARP) and then apoptosis. It also showed that BV induced S-phase arrest in MCF7 cells which may occur through the promotion of p53, p21, p27 and the exhibition of Cdk2. Western blotting demonstrated that BV reduced Bcl-2 and increased Bax protein levels which may have caused the changes of delta psi m. BV treatment led to ROS production up to but after treatment led to a decrease in the levels of ROS, which may be associated with the observations of BVaffecting glutathion S-transferase (GST), Zn-superoxide dismutase (Zn-SOD), Cu/Zn-superoxide dismutase (Cu/Zn-SOD) and catalase. The Comet assay also showed that BV induced DNA damage while DAPI staining also confirmed that BV induced apoptosis in examined MCF7 cells. Our results also showed that BV increased the levels of AIF and EndoG in MCF7 cells. In conclusion, our data demonstrated that BV induced apoptosis via a mitochondria-dependent pathway based on the changes of delta psi m, AIF and EndoG release in MCF7 cells.
 ...
PMID:The role of mitochondria in bee venom-induced apoptosis in human breast cancer MCF7 cells. 1846 9

In this study, we investigate the anticancer effect of isoobtusilactone A (IOA), a constituent isolated from the leaves of Cinnamomum kotoense, on human non-small cell lung cancer (NSCLC) A549 cells. IOA was found to induce the arrest of G2-M phase, induce apoptosis, increase sub-G1, and inhibit the growth of these cells. Further investigation revealed that IOA's blockade of the cell cycle was associated with increased levels of p21/WAF1, p27 (kip1), and p53. In addition, IOA triggered the mitochondrial apoptotic pathway, as indicated by an increase in Bax/Bcl-2 ratios, resulting in a loss of mitochondrial membrane potential, release of cytochrome c, activation of caspase-9 and caspase-3, and cleavage of PARP. We also found the generation of reactive oxygen species (ROS) to be a critical mediator in IOA-induced inhibition of A549 cell growth. In antioxidant and NO inhibitor studies, we found that by pretreating A549 cells with either N-acetylcystenine (NAC), catalase, mannitol, dexamethasone, trolox, or L-NAME we could significantly decrease IOA production of ROS. Moreover, using NAC to block ROS, we could significantly suppress IOA-induced antiproliferation, antimigration, and anti-invasion. Finally, we found that IOA inhibited the migration and invasion of A549 cell migration and invasion. Taken together, these results suggest that IOA has anticancer effects on A549 cells.
 ...
PMID:Anticancer activity of isoobtusilactone A from Cinnamomum kotoense: involvement of apoptosis, cell-cycle dysregulation, mitochondria regulation, and reactive oxygen species. 1848 63

The multifunctional, anti-Alzheimer drug, ladostigil (TV3326) [(N-propargyl-(3R) aminoindan-5yl)-ethyl methyl carbamate] combines the neuroprotective effects of the anti-Parkinson drug, rasagiline, a selective monoamine oxidase (MAO)-B inhibitor, with the cholinesterase (ChE) inhibitory activity of rivastigmine in a single molecule. Ladostigil has been shown to possess potent antiapoptotic and neuroprotective activities in various oxidative insults in vitro and in vivo, such as prevention of the fall in mitochondrial membrane potential and regulation of Bcl-2 family proteins. In the present study, we demonstrate that ladostigil (1 microM) increased cell viability, associated with the increase of catalase activity and decrease of intracellular reactive oxygen species (ROS) production in human SH-SY5Y neuroblastoma cells exposed to (hydrogen peroxide) H(2)O(2). Furthermore, ladostigil significantly elevated mRNA levels of the antioxidants enzymes, catalase, NAD(P)H quinone oxidoreductase 1 (NQO1) and peroxiredoxin 1 (Prx 1) in H(2)O(2)-treated SH-SY5Y cells. Chronic treatment with ladostigil (1 mg/kg gavage per day for 30 days) markedly up-regulated mRNA expression levels of various antioxidant enzymes in aged rat hippocampus (e.g. glutathione peroxidase precursor (GSHPX-P), glutathione S-transferase (GST) and glucose-6-phosphate dehydrogenase (G6PD)). These findings indicate that in addition to its multiple neuroprotective characteristics, ladostigil also possesses antioxidant properties, which might be beneficial for the treatment of oxidative stress (OS) in aging and age-associated neurodegenerative diseases.
 ...
PMID:The neuroprotective effect of ladostigil against hydrogen peroxide-mediated cytotoxicity. 1859 87


<< Previous 1 2 3 4 5 6 7 8 9 10