Apoptosis

Source: www.ncbi.nlm.nih.gov --- 44 minutes ago
Related Articles Acid Sphingomyelinase Amplifies Redox Signaling in Pseudomonas aeruginosa-Induced Macrophage Apoptosis. J Immunol. 2008 Sep 15;181(6):4247-54 Authors: Zhang Y, Li X, Carpinteiro A, Gulbins E Recent studies indicate that distinct membrane microdomains, also named lipid rafts, and ceramide play an important role in infectious biology. Ceramide forms larger ceramide-enriched membrane platforms that are required for diverse signal transduction. In this study, we demonstrate that ceramide-enriched membrane platforms are critically involved in redox signaling that regulates alveolar macrophage Apoptosis upon infection with Pseudomonas aeruginosa. In freshly isolated alveolar macrophages, P. aeruginosa infection results in rapid activation of acid sphingomyelinase (Asm), release of ceramide, and formation of ceramide-enriched membrane platforms, which are required for P. aeruginosa-induced activation of NADPH oxidase and production of reactive oxygen species (ROS). Inhibition of NADPH oxidase or removal of intracellular ROS reduced P. aeruginosa-induced activation of the Asm and formation of ceramide-enriched membrane platforms, suggesting that NADPH oxidase-derived ROS regulate Asm-initiated redox signaling in a positive feedback manner. Furthermore, stimulation of JNK and induction of Apoptosis upon P. aeruginosa infections are dependent on NADPH oxidase-derived ROS. These findings indicate that ceramide-enriched membrane pl ...

Source: www.ncbi.nlm.nih.gov --- 4 days ago
Related Articles miR-34a repression of SIRT1 regulates Apoptosis. Proc Natl Acad Sci U S A. 2008 Aug 28; Authors: Yamakuchi M, Ferlito M, Lowenstein CJ MicroRNA 34a (miR-34a) is a tumor suppressor gene, but how it regulates cell proliferation is not completely understood. We now show that the microRNA miR-34a regulates silent information regulator 1 (SIRT1) expression. MiR-34a inhibits SIRT1 expression through a miR-34a-binding site within the 3' UTR of SIRT1. MiR-34 inhibition of SIRT1 leads to an increase in acetylated p53 and expression of p21 and PUMA, transcriptional targets of p53 that regulate the cell cycle and Apoptosis, respectively. Furthermore, miR-34 suppression of SIRT1 ultimately leads to Apoptosis in WT human colon cancer cells but not in human colon cancer cells lacking p53. Finally, miR-34a itself is a transcriptional target of p53, suggesting a positive feedback loop between p53 and miR-34a. Thus, miR-34a functions as a tumor suppressor, in part, through a SIRT1-p53 pathway. PMID: 18755897 [PubMed - as supplied by publisher] ...

Source: www.ncbi.nlm.nih.gov --- 3 days ago
Related Articles [Effect of dioxin on Apoptosis of osteogenic sarcoma cells and regulation on gene expression of insulin-like growth factor binding protein 6] Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2008 Apr;26(4):223-6 Authors: Guo L, Zhao YY, Zhang SL, Liu K, Gao XY OBJECTIVE: To investigate the effect of the environmental carcinogenic factor-TCDD (2, 3, 7, 8-tetrachlorodibenzo-p-dioxin) on cell Apoptosis and gene regulation of insulin-like growth factor binding protein 6 (IGFBP-6) in osteogenic sarcoma (SaOS-2) cells. METHODS: The SaOS-2 cells were cultured with TCDD (1 x 10(-9), 1 x 10(-8), 1 x 10(-7) mol/L) for 24 hours. The MTT reduction assay and flow cytometry were used to measure the cell proliferation and the cell Apoptosis in TCDD-treated SaOS-2 cells. The Nitrophenol phosphate salt method was used to measure activity of alkaline phosphatase (ALP) in SaOS-2 cells. The IGFBP-6 mRNA and protein in SaOS-2 cells were detected by reverse transcription polymerase chain reaction (RT-PCR) and western blotting analysis. RESULTS: SaOS-2 cell proliferation was up-regulated with TCDD (1 x 10(-9), 1 x 10(-8), and 1 x 10(-7) mol/L) about 20%, 47% and 93% (18.4 +/- 4.5, 22.5 +/- 3.6 and 29.4 +/- 4.2), respectively. The synthesis of ALP was up-regulated about 28%, 95%, and 142% (1.12 +/- 0.28, 1.58 +/- 0.14 and 1.96 +/- 0.17), respectively (P < 0.05). The cell Apoptosis was down-regulated in dose-dependent biological manner about 5% ...

Source: www.ncbi.nlm.nih.gov --- 2 days ago
Related Articles Targeted manipulation of Apoptosis in cancer treatment. Lancet Oncol. 2008 Aug 27; Authors: Call JA, Eckhardt SG, Camidge DR Apoptosis is a fundamental process in the development and maintenance of multicellular organisms and its regulation is commonly disrupted in human cancers. In vitro and in vivo, effective treatment of cancer with radiotherapy or anticancer drugs (or both) is frequently associated with increased markers of Apoptosis. However, clinical resistance to treatment is common in many tumours, particularly with increasing lines of therapy. Diminished ability to undergo Apoptosis might cause extensive therapeutic cross-resistance in cancer cells. With increased understanding of the regulatory and effector molecules of Apoptosis new drugs have been developed that might manipulate the apoptotic balance in cancer cells in favour of cell death. This Review summarises the rationale for direct manipulation of various elements of Apoptosis and describes agents that are currently under investigation in early-phase clinical trials in many different cancer types. PMID: 18760670 [PubMed - as supplied by publisher] ...

Source: www.ncbi.nlm.nih.gov --- 2 days ago
Related Articles ADENOVIRUS-MEDIATED FKBP12.6 OVEREXPRESSION INDUCES HYPERTROPHY AND Apoptosis IN CULTURED NEONATAL CARDIOMYOCYTES. Clin Exp Pharmacol Physiol. 2008 Aug 26; Authors: Zhong J, Chen J, Cao T, Wang L, Zhang W, Liu D, Zhu Z 1. Cardiac ryanodine RyR2 receptors regulate Ca(2+) release from the sarcoplasmic reticulum (SR). FK506 binding protein (FKBP) 12.6 prevents aberrant SR Ca(2+) leakage during diastole, thereby maintaining the integrity of RyR2 function. Previous studies have focused mainly on FKBP12.6 deficiency and so the pathophysiological consequences of FKBP12.6 overexpression remain unclear. Herein, we investigate the effect of FKBP12.6 overexpression on cardiac hypertrophic and apoptotic signalling. 2. Human FKBP12.6 cDNA was cloned into pAdTrack-CMV and the resulting plasmid, along with a control empty plasmid, were transfected into bacteria. The resulting virus, namely Ad-FKBP12.6 containing green fluorescent protein, was propagated and purified. Neonatal rat cardiomyocytes were infected with this virus. Protein and DNA synthesis were measured by [(3)H]-leucine and [(3)H]-thymidine incorporation, respectively. Expression of p38 mitogen-activated protein kinase (MAPK), phosphorylated extracellular signal-regulated kinase 1 or 2 (p-ERK1/2) and Bax were examined by western blotting. 3. Compared with control cells, cardiomyocytes that overexpressed FKBP12.6 became hypertrophic and hyperplastic, with increased levels ...

Source: www.ncbi.nlm.nih.gov --- 16 hours ago
Related Articles Construction of a cancer-perturbed protein-protein interaction network for discovery of Apoptosis drug targets. BMC Syst Biol. 2008;2:56 Authors: Chu LH, Chen BS BACKGROUND: Cancer is caused by genetic abnormalities, such as mutations of oncogenes or tumor suppressor genes, which alter downstream signal transduction pathways and protein-protein interactions. Comparisons of the interactions of proteins in cancerous and normal cells can shed light on the mechanisms of carcinogenesis. RESULTS: We constructed initial networks of protein-protein interactions involved in the Apoptosis of cancerous and normal cells by use of two human yeast two-hybrid data sets and four online databases. Next, we applied a nonlinear stochastic model, maximum likelihood parameter estimation, and Akaike Information Criteria (AIC) to eliminate false-positive protein-protein interactions in our initial protein interaction networks by use of microarray data. Comparisons of the networks of Apoptosis in HeLa (human cervical carcinoma) cells and in normal primary lung fibroblasts provided insight into the mechanism of Apoptosis and allowed identification of potential drug targets. The potential targets include BCL2, caspase-3 and TP53. Our comparison of cancerous and normal cells also allowed derivation of several party hubs and date hubs in the human protein-protein interaction networks involved in caspase activation. CONCLUSION: Our method allows i ...

Source: www.ncbi.nlm.nih.gov --- 6 hours ago
Related Articles Soluble amyloid beta oligomers may contribute to Apoptosis of retinal ganglion cells in glaucoma. Med Hypotheses. 2008;71(1):77-80 Authors: Yin H, Chen L, Chen X, Liu X Glaucoma is one of the leading causes of visual impairment and blindness. It is characterized by excavation of optic nerve head and visual field loss. Even though the pathogenesis of glaucoma remains unclear, it is generally accepted that elevated intraocular pressure is the major risk factor. No matter what the specific initiators are, retinal ganglion cells are believed to die via Apoptosis eventually. It is known that glaucoma correlates strongly with Alzheimer's disease and the two diseases share many similarities in pathogenic mechanisms. Recent studies have indicated that amyloid beta peptide, which is implicated in the progression of Alzheimer's disease, may be also responsible for retinal ganglion cells death in glaucoma. Amyloid beta exists in different forms, including monomers, oligomers and fibrils, and among these, as demonstrated by extensive evidences, soluble amyloid beta oligomers rather than insoluble amyloid beta fibrils induced Apoptosis of neurons in Alzheimer's disease. Here we propose that soluble amyloid beta oligomers may play an important role in activation of apoptotic cascades in retinal ganglion cells in glaucoma. PMID: 18406539 [PubMed - indexed for MEDLINE] ...

Source: www.ncbi.nlm.nih.gov --- 5 hours ago
Related Articles Statins induce Apoptosis in ovarian cancer cells through activation of JNK and enhancement of Bim expression. Cancer Chemother Pharmacol. 2008 Sep 3; Authors: Liu H, Liang SL, Kumar S, Weyman CM, Liu W, Zhou A PURPOSE: Ovarian cancer is the leading cause of death among all gynecological malignancies in Western countries. Although therapy for ovarian cancer has been greatly improved in the past 20 years, the overall survival for patients with advanced ovarian cancer has not changed significantly. The poor survival rates in patients with advanced ovarian cancer are due both to late diagnosis and to lack of effective drugs for the majority of patients who have a relapse and develop resistance to current chemotherapy agents used for ovarian cancer. Thus, developing and discovering effective novel drugs with different molecular structures from conventional chemotherapy agents have become an urgent clinical need. METHODS: Ovarian cancer cells were treated with lovastatin and atorvastatin. Apoptosis in these cells and tumor formation in soft agar were determined. The molecular mechanism by which statins suppress ovarian cancer cell growth was evaluated. RESULTS: Both lovastatin and atorvastatin effectively induced Apoptosis in ovarian cancer cells and suppressed anchorage-independent growth of these cells in soft agar. Further investigation of the molecular mechanism has revealed that the expression of Cdc42 and Rac1, small GT ...

Source: www.ncbi.nlm.nih.gov --- 3 days ago
Related Articles Thyroid hormone-mediated activation of the ERK/DUSP1 pathway augments the Apoptosis of GH4C1 cells by down-regulating NF-{kappa}B activity. Mol Endocrinol. 2008 Aug 28; Authors: Chiloeches A, Sánchez-Pacheco A, Gil-Araujo B, Aranda A, Lasa M Thyroid hormone (T3) plays a crucial role in processes such as cell proliferation and differentiation, while its implication on cellular Apoptosis has not been well documented. Here we examined the effect of T3 on the Apoptosis of GH4C1 pituitary cells and the mechanisms underlying this effect. We show that T3 produced a significant increase in Apoptosis in serum-depleted conditions. This effect was accompanied by a decrease in NF-kappaB-dependent transcription, IkappaBalpha phosphorylation, translocation of p65/NF-kappaB to the nucleus, phosphorylation, and transactivation. Moreover, these effects were correlated with a T3-induced decrease in the expression of anti-apoptotic gene products, such as members of the IAP and Bcl-2 families. On the other hand, ERK but not JNK or MAPK p38, was activated upon exposure to T3, and inhibition of ERK alone abrogated T3-mediated Apoptosis. In addition T3 increased the expression of the MAPK phosphatase, DUSP1, in an ERK-dependent manner. Interestingly, the suppression of DUSP1 expression abrogated T3-induced inhibition of NF-kappaB-dependent transcription and p65/NF-kappaB translocation to the nucleus, as well as T3-mediated Apoptosis. Overall, ...

Source: www.ncbi.nlm.nih.gov --- 1 day ago
Related Articles Rapid reactive oxygen species (ROS) generation induced by curcumin leads to caspase-dependent and -independent Apoptosis in L929 cells. Free Radic Biol Med. 2008 Aug 16; Authors: Thayyullathil F, Chathoth S, Hago A, Patel M, Galadari S Evidence that curcumin may have anticancer activities has renewed interest in its potential to prevent and treat disease. In this study, we show that curcumin-mediated rapid generation of reactive oxygen species (ROS) leads to Apoptosis by modulating different apoptotic pathways in mouse fibroblast L929 cells. We show for the first time that curcumin-induced rapid ROS generation causes the release of Apoptosis inducing factor (AIF) from the mitochondria to the cytosol and nucleus, hence, leading to caspase 3-independent Apoptosis. However, our studies also show that curcumin induces the release of cytochrome c from mitochondria, causing activation of caspase 3, and concomitant PARP cleavage, which is the hallmark of caspase-dependent Apoptosis. Furthermore, curcumin-induced ROS generation leads to the induction of the proapoptotic protein p53 and its effector protein p21 and down-regulation of cell cycle regulatory proteins such as Rb and cyclin D1 and D3. Both glutathione (GSH) and N-acetylcysteine (NAC) pretreatment resulted in the complete inhibition of curcumin-induced ROS generation, AIF release from mitochondria, and caspase activation. Additionally, pretreatment of L929 cells with ...

Source: www.ncbi.nlm.nih.gov --- 15 days ago
Related Articles Involvement of Miltefosine mediated ERK activation in glioma cell Apoptosis through Fas regulation. J Neurochem. 2008 Aug 14; Authors: Tewari R, Sharma V, Koul N, Sen E The anti-neoplastic property of alkyl phospholipids (ALPs) has been tested for the treatment of several malignancies. In this study we evaluated the efficacy of Miltefosine (Hexadecylphosphocholine - an ALP analogue) on glioblastoma multiforme (GBM). Here we demonstrate that Miltefosine induced Apoptosis is accompanied by elevated Fas, Fas associated death domain (FADD) expression, caspase-8 activity and the increased distribution of Fas and FADD towards lipid raft microdomain to form death inducing signaling complex (DISC). Treatment with Miltefosine resulted in increase in Ras, extracellular signal-regulated kinase (ERK) and p38MAPK activity. Expression of dominant-negative Ras (Ras N17) attenuated Miltefosine mediated Apoptosis. Although inhibition of both ERK and p38MAPK decreased the pro-apoptotic effects of Miltefosine, it was the inhibition of ERK and not p38MAPK activation that decreased Fas and FADD expression. An ERK dependent increase in the expression of gammaH2AX-involved in response to DNA double stranded breaks was also observed. Taken together, our findings suggest the involvement of ERK activation in Miltefosine induced glioma cell Apoptosis. PMID: 18710416 [PubMed - as supplied by publisher] ...

Source: www.ncbi.nlm.nih.gov --- 16 days ago
Related Articles [Protein kinase C inhibitor Gö6976 sensitizes arsenic trioxide-induced cell Apoptosis in chronic myeloid leukemic cells] Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2005 Feb;13(1):100-3 Authors: Wu XF, Chen ZC, Liu ZP, You Y, Li WM, Zou P To investigate the As(2)O(3)-chemosensitization of Gö6976 in K562 cells by its abrogation of As(2)O(3)-induced G(2)/M cell cycle arrest, K562 cells were treated with As(2)O(3) (5 micromol/L) and Gö6976 with various concentrations, the distributions of cell cycles were detected by flow cytometry, the cell viability was observed by trypan blue exclusion test and cell proliferation was tested by MTT assay. The results indicated that having treated by As(2)O(3) for 24 h and 48 h, the proportion of K562 cells in G(2)/M phase were (38.02 +/- 7.70)% and (32.58 +/- 7.43)% respectively, and no obvious cell Apoptosis appeared. 50 nmol/L Gö6976 combined with As(2)O(3) decrease the proportion of cells in G(2)/M phase to (23.24 +/- 2.93)% and (16.18 +/- 1.60)% respectively and increase the proportion of cells in subG(1) phase to (11.82 +/- 2.31)% and (27.80 +/- 2.89)% respectively. Gö6976 abrogated G(2)/M cell cycle arrest induced by As(2)O(3) and increased cell Apoptosis in a concentration- and time-dependent manner. Additionally, comparing to the control group, Gö6976 combined with As(2)O(3) decreased the cell viability and depressed the cell proliferation, but Gö6976 alone showed no same effect on them ...

Source: www.ncbi.nlm.nih.gov --- 19 days ago
Related Articles Induction of Apoptosis by intrapleural perfusion hyperthermo-chemotherapy for malignant pleural mesothelioma. Ann Thorac Cardiovasc Surg. 2008 Jun;14(3):161-5 Authors: Matsuzaki Y, Tomita M, Shimizu T, Hara M, Ayabe T, Onitsuka T PURPOSE: Despite extensive clinical research, no effective therapy for advanced malignant pleural mesothelioma has been established. In this study, we induced Apoptosis in patients with this disease, using intrapleural perfusion hyperthermo-chemotherapy, a new procedure developed in our surgical department. We then measured the tumorcidal effect. MATERIAL AND METHODS: Our study included 6 consecutive patients with malignant pleural mesothelioma (stage III: 5; stage IV: 1). Because of the advanced stage of the disease, none of the patients underwent tumor resection or pleurectomy. All patients, however, received perfusion treatment. Tumor cells collected from pleural effusions pre-and at 0, 24, and 48 h postperfusion were examined using an immunocytochemical stain to determine Apoptosis. The percentage of positively stained cells was expressed as the apoptotic index. RESULTS: Preperfusion, the apoptotic index was 3.8%+/-2.0%, indicating spontaneous Apoptosis of untreated tumor cells. Postperfusion, the apoptotic index at 0, 24, and 48 h was 22.8%+/-5.15%, 63.8%+/-8.2%, and 47.8%+/-6.9%, respectively. The patients had a median survival time of 30 months. No patient morbidity was associated with ...

Source: www.ncbi.nlm.nih.gov --- 21 days ago
Related Articles Effects of Apoptosis and lipid peroxidation on T-lymphoblastoid phospholipid-dependent procoagulant activity. J Thromb Haemost. 2008 Jul;6(7):1122-30 Authors: Pickering W, Gray E, Goodall AH, Barrowcliffe TW BACKGROUND: Coagulation has an absolute requirement for macromolecular complexes to be assembled on a negatively charged phospholipid (PL) surface. Previously, we reported that malignant T-lymphoblastoid cells have the ability to support procoagulant activity (PCA) independently of tissue factor by providing such a surface. OBJECTIVE: To explore the effect of two pathophysiologic processes, Apoptosis and lipid peroxidation (LP), on this PL-dependent PCA. METHODS: Three different assays for PL-dependent PCA (factor IXa-initiated FXa and thrombin generation and prothrombinase activity) were used to investigate this PCA after exposing three T-lymphoblastoid cell lines to either apoptotic stimuli (1 microM staurosporine) or oxidative stress (4 mm H(2)O(2) and 40 microM CuSO(4)). Surface exposure of anionic PL was measured by flow cytometry using annexin A5(FITC) and an antibody (3G4) specific for native, but not oxidized, phosphatidylserine (PS). RESULTS AND CONCLUSIONS: Both Apoptosis and LP significantly enhanced the PCA of cells, to a level that was greater than that observed following calcium ionophore treatment, suggesting that the increased activity was not solely due to anionic PL exposure. Whereas cells undergo ...

Source: www.ncbi.nlm.nih.gov --- 20 days ago
Related Articles Octamer 4 small interfering RNA results in cancer stem cell-like cell Apoptosis. Cancer Res. 2008 Aug 15;68(16):6533-40 Authors: Hu T, Liu S, Breiter DR, Wang F, Tang Y, Sun S Octamer 4 (Oct4), a member of the POU family of transcription factors, plays a key role in the maintenance of pluripotency and proliferation potential of embryonic stem cells. Cancer stem cell-like cells (CSCLC) are reported to be a minor population in tumors or even in tumor cell lines which also express Oct4. The role of Oct4 in CSCLCs still remains to be defined. In our study, we show that, in vitro, almost all murine Lewis lung carcinoma 3LL cells and human breast cancer MCF7 cells express Oct4 at high levels. This expression of Oct4 is successfully reduced by small interfering RNA, which eventually results in cell Apoptosis. The signal pathway Oct4/Tcl1/Akt1 has been observed to be involved in this event. The repression of Oct4 reduces Tcl1 expression and further down-regulates the level of p-Ser.473-Akt1. In vivo, only approximately 5% of tumor cells were detected to express Oct4 in established 3LL and MCF7 tumor models, respectively. Small interfering RNA against Oct4 successfully decreases the CSCLCs and markedly inhibits tumor growth. In summary, we show that Oct4 might maintain the survival of CSCLCs partly through Oct4/Tcl1/Akt1 by inhibiting Apoptosis, which strongly indicates that targeting Oct4 may have important clinical applicati ...

Source: www.ncbi.nlm.nih.gov --- 34 days ago
Related Articles Requirement of a functional spindle checkpoint for arsenite-induced Apoptosis. J Cell Biochem. 2008 Jul 30; Authors: Wu YC, Yen WY, Yih LH To understand the potential influence of spindle checkpoint function in response to arsenic trioxide (ATO)-induced Apoptosis observed in cancer cell lines, we examined the correlation between activation of the spindle checkpoint and susceptibility to ATO-induced Apoptosis in 10 cancer cell lines lacking functional p53. The ability to functionally activate the spindle checkpoint in each cancer cell line was assessed by the induction of mitotic arrest after Taxol treatment. Bromodeoxyuridine (BrdU) pulse-chase analysis of Taxol-treated cell lines with low mitotic arrest showed that they were not arrested at mitosis but divided abnormally, confirming that spindle checkpoint activation was impaired in these cell lines. Our results demonstrate that Apoptosis was significantly induced by ATO in cancer cell lines with functional activation of the spindle checkpoint and substantial induction of mitotic arrest. Cell lines with negligible mitotic arrest exhibited little ATO-induced Apoptosis. However, no such correlation was observed following treatment of cells with camptothecin, a topoisomerase I inhibitor. Furthermore, attenuation of the spindle checkpoint function by small interfering RNA-mediated silencing of BubR1 and Mad2 in cancer cells that were susceptible to ATO-induced mitotic arr ...

Source: www.ncbi.nlm.nih.gov --- 29 days ago
Related Articles Role of nuclear bodies in Apoptosis signalling. Biochim Biophys Acta. 2008 Jul 16; Authors: Krieghoff-Henning E, Hofmann TG Promyelocytic leukemia nuclear bodies (PML NBs) are dynamic macromolecular multiprotein complexes that recruit and release a plethora of proteins. A considerable number of PML NB components play vital roles in Apoptosis, senescence regulation and tumour suppression. The molecular basis by which PML NBs control these cellular responses is still just beginning to be understood. In addition to PML itself, numerous further tumour suppressors including transcriptional regulator p53, acetyl transferase CBP (CREB binding protein) and protein kinase HIPK2 (homeodomain interacting protein kinase 2) are recruited to PML NBs in response to genotoxic stress or oncogenic transformation and drive the senescence and Apoptosis response by regulating p53 activity. Moreover, in response to death-receptor activation, PML NBs may act as nuclear depots that release apoptotic factors, such as the FLASH (FLICE-associated huge) protein, to amplify the death signal. PML NBs are also associated with other nuclear domains including Cajal bodies and nucleoli and share apoptotic regulators with these domains, implying crosstalk between NBs in Apoptosis regulation. In conclusion, PML NBs appear to regulate cell death decisions through different, pathway-specific molecular mechanisms. PMID: 18680765 [PubMed - as supplied by pub ...

Source: www.ncbi.nlm.nih.gov --- 26 days ago
Related Articles Granulysin Produced by Uterine Natural Killer Cells Induces Apoptosis of Extravillous Trophoblasts in Spontaneous Abortion. Am J Pathol. 2008 Aug 7; Authors: Nakashima A, Shiozaki A, Myojo S, Ito M, Tatematsu M, Sakai M, Takamori Y, Ogawa K, Nagata K, Saito S Immune changes are known to occur in recurrent spontaneous abortion, but it is unclear whether either maternal natural killer (NK) cells or T cells attack fetus-derived trophoblasts. To clarify the immunological causes of spontaneous abortion, we examined the relationship between cytotoxic granule proteins in decidual lymphocytes, such as granulysin, granzyme B, and perforin, and the induction of Apoptosis in extravillous trophoblasts (EVTs). The number of granulysin-positive CD56(bright) NK cells increased significantly in the decidua basalis during spontaneous abortion compared with normal pregnancy; however, granzyme B- and perforin-positive cells did not change. Interestingly, the expression of granulysin was also detected in the nuclei of EVTs in spontaneous abortion samples. When IL-2-stimulated CD56(bright) NK cells were cocultured with EVT cells (HTR-8/SV40neo), granulysin was found initially in the cytoplasm and then accumulated in the nuclei of the HTR-8/SV40neo cells. Furthermore, transfected cells expressing a GFP-granulysin fusion protein induced Apoptosis in HTR-8/SV40neo cells independently of caspases. Our results suggest that granulysin-positive u ...

Source: www.ncbi.nlm.nih.gov --- 25 days ago
Related Articles Resveratrol induces Apoptosis and inhibits adipogenesis in 3T3-L1 adipocytes. Phytother Res. 2008 Aug 7; Authors: Rayalam S, Yang JY, Ambati S, Della-Fera MA, Baile CA Resveratrol, a phytoallexin, has recently been reported to slow aging by acting as a sirtuin activator. Resveratrol also has a wide range of pharmacological effects on adipocytes. In this study, we investigated the effects of resveratrol on adipogenesis and Apoptosis using 3T3-L1 cells. In mature adipocytes, 100 and 200 microM resveratrol decreased cell viability dose-dependently by 23 +/- 2.7%, and 75.3 +/- 2.8% (p < 0.0001), respectively, after 48 h treatment, and 100 microM resveratrol increased Apoptosis by 76 +/- 8.7% (p < 0.0001). Resveratrol at 25 and 50 microM decreased lipid accumulation in maturing preadipocytes significantly by 43 +/- 1.27% and 94.3 +/- 0.3% (p < 0.0001) and decreased cell viability by 25 +/- 1.3% and 70.4 +/- 1.6% (p < 0.0001), respectively. In order to understand the anti-adipogenic effects of resveratrol, maturing 3T3-L1 preadipocytes were treated with 25 microM resveratrol and the change in the expression of several adipogenic transcription factors and enzymes was investigated using real-time RT-PCR. Resveratrol down-regulated the expression of PPARgamma, C/EBPalpha, SREBP-1c, FAS, HSL, LPL and up-regulated the expression of genes regulating mitochondrial activity (SIRT3, UCP1 and Mfn2). These results indicate that resver ...

Source: www.ncbi.nlm.nih.gov --- 25 days ago
Related Articles Neuronal Apoptosis and Autophagy Cross Talk in Aging PS/APP Mice, a Model of Alzheimer's Disease. Am J Pathol. 2008 Aug 7; Authors: Yang DS, Kumar A, Stavrides P, Peterson J, Peterhoff CM, Pawlik M, Levy E, Cataldo AM, Nixon RA Mechanisms of neuronal loss in Alzheimer's disease (AD) are poorly understood. Here we show that Apoptosis is a major form of neuronal cell death in PS/APP mice modeling AD-like neurodegeneration. Pyknotic neurons in adult PS/APP mice exhibited apoptotic changes, including DNA fragmentation, caspase-3 activation, and caspase-cleaved alpha-spectrin generation, identical to developmental neuronal Apoptosis in wild-type mice. Ultrastructural examination using immunogold cytochemistry confirmed that activated caspase-3-positive neurons also exhibited chromatin margination and condensation, chromatin balls, and nuclear membrane fragmentation. Numbers of apoptotic profiles in both cortex and hippocampus of PS/APP mice compared with age-matched controls were twofold to threefold higher at 6 months of age and eightfold higher at 21 to 26 months of age. Additional neurons undergoing dark cell degeneration exhibited none of these apoptotic features. Activated caspase-3 and caspase-3-cleaved spectrin were abundant in autophagic vacuoles, accumulating in dystrophic neurites of PS/APP mice similar to AD brains. Administration of the cysteine protease inhibitor, leupeptin, promoted accumulation of autophagic ...