Bcl2 like killer

Di(2-ethylhexyl) phthalate (DEHP) is a ubiquitous environmental toxicant found in consumer products that causes ovarian toxicity. Antral follicles are the functional ovarian units and must undergo growth, survival from atresia, and proper regulation of steroidogenesis to ovulate and produce hormones. Previous studies have determined that DEHP inhibits antral follicle growth and decreases estradiol levels in vitro; however, the mechanism by which DEHP elicits these effects is unknown. The present study tested the hypothesis that DEHP directly alters regulators of the cell cycle, apoptosis, and steroidogenesis to inhibit antral follicle functionality...

Intrinsic apoptotic stimuli initiate mammalian cells' apoptotic program by first activating the proteins that have only Bcl-2 homology domain 3 (BH3), such as Bcl-2 interacting mediator of cell death (Bim) and truncated BH3 interacting death domain agonist (tBid), which in turn trigger conformational changes in BCL2-associated X (Bax) and BCL2-antagonist/killer (Bak) proteins that enable oligomer formation on the mitochondria, causing cytochrome c and other apoptogenic proteins in the intermembrane space to leak out...

Reactive astrogliosis is a cellular manifestation of neuroinflammation and occurs in response to all forms and severities of the central nervous system (CNS)'s injury and disease. Both astroglial proliferation and antiapoptotic processes are aspects of astrogliosis. However, the underlying mechanism of this response remains poorly understood. In addition, little is known about why activated astrocytes are more resistant to stress and inflammation. CCAAT/enhancer binding protein delta (CEBPD) is a transcription factor found in activated astrocytes that surround β-amyloid plaques...

HMG-CoA reductase, the proximal rate-limiting enzyme in the mevalonate pathway, is inhibited by statins. Beyond their cholesterol lowering impact, statins have pleiotropic effects and their use is linked to improved lung health. We have shown that mevalonate cascade inhibition induces apoptosis and autophagy in cultured human airway mesenchymal cells. Here, we show that simvastatin also induces endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) in these cells. We tested whether coordination of ER stress, autophagy and apoptosis determines survival or demise of human lung mesenchymal cells exposed to statin...

Innate immune and inflammatory responses mediated by Toll like receptors (TLRs) have been implicated in myocardial ischemia/reperfusion (I/R) injury. This study examined the role of TLR3 in myocardial injury induced by two models, namely, myocardial infarction (MI) and I/R. First, we examined the role of TLR3 in MI. TLR3 deficient (TLR3(-/-)) and wild type (WT) mice were subjected to MI induced by permanent ligation of the left anterior descending (LAD) coronary artery for 21days. Cardiac function was measured by echocardiography...

Oncogenic transcription factor Myc deregulates the cell cycle and simultaneously reprograms cellular metabolism to meet the biosynthetic and bioenergetic needs of proliferation. Myc also sensitizes cells to mitochondria-dependent apoptosis. Although metabolic reprogramming has been circumstantially connected to vulnerability to apoptosis, the connecting molecular pathways have remained poorly defined. Here, we show that Myc-induced altered glutamine metabolism involves ATP depletion and activation of the energy sensor AMP-activated protein kinase (AMPK), which induces stabilizing phosphorylation of p53 at Ser15...

Determining mechanistic details about how drugs kill cancer cells is critical for predicting which cancers will respond to given therapeutic regimens and for identifying effective combinations of drugs that more potently kill cancer cells while sparing normal cells. The BCL2 family of proteins and bioactive sphingolipids are intricately linked during apoptotic cell death. In fact, many chemotherapeutic drugs are known to cause accumulation of the pro-apoptotic sphingolipid ceramide; however, the mechanism by which this occurs is not completely understood...

The fate of Foxp3(+) regulatory T (Treg) cells responding during autoimmunity is not well defined. We observed a marked elevation in KLRG1(+) (where KLRG1 stands for killer cell lectin-like receptor G1) CNS-infiltrating Treg cells in experimental autoimmune encephalomyelitis (EAE), and assessed their origin and properties. KLRG1(+) Treg cells showed increased activation marker expression, Foxp3 and CD25 levels, and more rapid cell cycling than KLRG1(-) cells. KLRG1(-) Treg cells converted into KLRG1(+) cells and this was increased in autoimmune inflammation...

Bap31 is an integral ER membrane protein which functions as an escort factor in the sorting of newly synthesized membrane proteins within the endoplasmic reticulum (ER). During apoptosis signaling, Bap31 is subject to early cleavage by initiator caspase-8. The resulting p20Bap31 (p20) fragment has been shown to initiate proapoptotic ER-mitochondria Ca2+ transmission, and to exert dominant negative (DN) effects on ER protein trafficking. We now report that ectopic expression of p20 in E1A/DNp53-transformed baby mouse kidney epithelial cells initiates a non-apoptotic form of cell death with paraptosis-like morphology...

BACKGROUND/AIMS: Hedgehog (Hh) pathway has been considered as a therapy target for various cancer entities. However, its mechanism in colorectal cancer is still unclear. METHODOLOGY: We analyzed the expression of Hh pathway members in colorectal adenomas and cancer cell lines and then studied its relationship with survival of colorectal cancer cells through inhibiting Hh pathway by cyclopamine. Moreover, we studied the regulation of Gli1 on insulin-like growth factor binding protein 6 (IGFBP6) and B-cell CLL/lymphoma 2 (Bcl-2) genes at the level of transcription by XChIP and cyclopamine inhibition assay...

OBJECTIVE: Increasing evidence suggests an association between periodontal disease and low birthweight (LBW); however the underlying molecular mechanisms are yet to be fully elucidated. In this study, we performed a microarray analysis to observe the human placental trophoblast-like BeWo cells response to lipopolysaccharide (LPS) from periodontopathogen Aggregatibacter actinomycetemcomitans (Aa), in order to investigate the molecular basis of mechanisms for periodontitis-associated LBW...

Members of the Bcl-2 family play key roles as proapoptotic (e.g., Bax) and antiapoptotic (e.g., Bcl-x(L)) regulators of programmed cell death. We previously identified the mitochondrial potassium channel Kv1.3 as a novel target of Bax. Incubating Kv1.3-positive isolated mitochondria with Bax triggered apoptotic events, whereas Kv1.3-deficient mitochondria were resistant to this stimulus. Mutation of Bax at lysine 128 (BaxK128E) abrogated its effects on Kv1.3 and the induction of apoptotic changes in mitochondria...

Lymphoid differentiation and activation critically depend on cytokine stimulation and the interleukin-7 (IL-7) signaling in particular. Although it has been demonstrated that IL-7 may play a role in natural killer (NK) cell maturation, the effect of IL-7 stimulation on mature human NK cells has not been studied. We, therefore, investigated the expression and functional activity of IL-7Ralpha on mature NK populations from adult blood. In this article, we demonstrate that IL-7Ralpha is specifically expressed in the CD56bright noncytotoxic cytokine-producing NK subset...

The Bcl2-interacting killer (BIK) gene interacts with cellular and viral survival-promoting proteins, such as Bcl-2, to enhance apoptosis. The BIK protein promotes cell death in a manner analogous to Bcl-2-related death-promoting proteins, Bax and Bak. There have been lower Bcl-2 levels and increased Bax/Bcl-2 ratio in the temporal cortex of patients with schizophrenia compared with those in controls. Because the death-promoting activity of BIK was suppressed in the presence of the cellular and viral survival-promoting proteins, the BIK protein is suggested as a likely target for antiapoptotic proteins...

Several inhibitors of BCL2 proteins have been identified that induce apoptosis in a variety of tumor cells, indicating their potential in cancer therapy. We investigated the specificity of six putative BCL2 inhibitors (obatoclax, gossypol, apogossypol, EM20-25, chelerythrine and ABT-737). Using cells deficient either for Bax/Bak or caspase-9, we found that only ABT-737 specifically targeted BCL2 proteins and induced apoptosis by activation of caspase-9, as only ABT-737 induced apoptosis was completely inhibited in cells deficient for Bax/Bak or caspase-9...

BACKGROUND: Overall mRNA expression analysis of colon biopsies can contribute to the understanding of molecular background of the local alterations and gene ontology-based functional classification of colonic biopsies into inflammatory and neoplastic diseases. METHODS: Total RNA was extracted from frozen biopsies and amplified by T7-method. Expression profile was evaluated by Atlas Glass 1K microarrays. After microarray quality control, applicable data were available from 10 adenomas, 6 colorectal adenocarcinoma (CRC), and inflammatory bowel diseases (IBDs: 3-3 CD and UC)...

AIM: To understand the local pathophysiological alterations and gene ontology-based functional classification of colonic biopsies into inflammatory and neoplastic diseases. METHODS: Total RNA was extracted from frozen biopsies and amplified by T7-method. Expression profile was evaluated by Atlas Glass 1K microarrays. After microarray quality control, applicable data were available from 10 adenomas, 6 colorectal adenocarcinomas (CRCs), and 6 inflammatory bowel diseases (IBDs)...

Parathyroid hormone-like hormone (PTHLH) secretion has been reported in human amnion, chorion, decidual cytotrophoblast, syncytiotrophoblast, endometrium, and myometrium; however, the functions of PTHLH during pregnancy, particularly during placenta formation and fetal development, are not well understood. We examined whether neutralization of PTHLH action using PTHLH antagonist, PTHLH(7-34), in rats during early gestation affects fetal and placental growth. Rats received s.c. a daily dose of either 0, 4, 12, or 36 microg of PTHLH(7-34) infused continuously through mini-osmotic pumps from Day 8 through Day 15 of pregnancy...

The aim of this study was to analyze the relations between differentiation immunophenotypes and the status of apoptosis and proliferation in diffuse large B-cell lymphomas. Therefore, the bcl6/CD10/MUM1/CD138 differentiation immunophenotypic profiles were studied in relation to (a) the apoptotic index, (b) the apoptosis-associated bcl2 family proteins bcl2, bcl-xl, bax, bak, bad and bid, (c) the proliferation index (Ki67) and (d) the cell cycle proteins cyclin A, cyclin B1, cyclin D3, cyclin E, p53, Rb, p16 and p27 in 79 cases of diffuse large B-cell lymphomas...

In this study, we have analyzed changes induced by hypoxia at the transcriptional level of genes that could be responsible for a more aggressive phenotype. Using a series of DNA array membranes, we identified a group of hypoxia-induced genes that included plasminogen activator inhibitor-1 (PAI-1), insulin-like growth factor-binding protein 3 (IGFBP-3), endothelin-2, low-density lipoprotein receptor-related protein (LRP), BCL2-interacting killer (BIK), migration-inhibitory factor (MIF), matrix metalloproteinase-13 (MMP-13), fibroblast growth factor-3 (FGF-3), GADD45, and vascular endothelial growth factor (VEGF)...