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Bcl2 like killer

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https://www.readbyqxmd.com/read/27678524/a-microtubule-inhibitor-abt-751-induces-autophagy-and-delays-apoptosis-in-huh-7-cells
#1
Ren-Jie Wei, Su-Shuan Lin, Wen-Ren Wu, Lih-Ren Chen, Chien-Feng Li, Han-De Chen, Chien-Ting Chou, Ya-Chun Chen, Shih-Shin Liang, Shang-Tao Chien, Yow-Ling Shiue
The objective was to investigate the upstream mechanisms of apoptosis which were triggered by a novel anti-microtubule drug, ABT-751, in hepatocellular carcinoma-derived Huh-7 cells. Effects of ABT-751 were evaluated by immunocytochemistry, flow cytometric, alkaline comet, soft agar, immunoblotting, CytoID, green fluorescent protein-microtubule associated protein 1 light chain 3 beta detection, plasmid transfection, nuclear/cytosol fractionation, coimmunoprecipitation, quantitative reverse transcription-polymerase chain reaction, small-hairpin RNA interference and mitochondria/cytosol fractionation assays...
September 24, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/26662110/breast-cancer-cell-line-mda-mb-231-mirna-profile-expression-after-bik-interference-bik-involvement-in-autophagy
#2
Ruth Ruiz Esparza-Garrido, María Eugenia Torres-Márquez, Rubí Viedma-Rodríguez, Ana Claudia Velázquez-Wong, Fabio Salamanca-Gómez, Haydeé Rosas-Vargas, Miguel Ángel Velázquez-Flores
B-cell lymphoma 2 (BCL2)-interacting killer (apoptosis inducing) (BIK) has been proposed as a tumor suppressor in diverse types of cancers. However, BIK's overexpression in breast cancer (BC) and in non-small lung cancer cells (NSCLCs), associated with a poor prognosis, suggests its participation in tumor progression. In this study, we evaluated the global expression pattern of microRNAs (miRNAs), messenger RNA (mRNA) expression changes in autophagy, and autophagic flux after BIK interference. BIK gene expression was silenced by small interfering RNA (siRNA) in BC cell MDA-MB-231, and BIK interference efficiency was tested by real-time PCR and by Western blotting...
May 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/26253785/bnip3-and-bnip3l-mediated-mitophagy-promotes-the-generation-of-natural-killer-cell-memory
#3
Timothy E O'Sullivan, Lexus R Johnson, Helen H Kang, Joseph C Sun
Natural killer (NK) cells are innate lymphocytes that possess traits of adaptive immunity, such as clonal expansion, contraction, and generation of long-lived "memory" cells, processes poorly understood at the molecular level. Here, we found that as proliferating NK cells accumulated dysfunctional mitochondria during viral infection, a protective mitophagy pathway was induced during the contraction phase to promote their survival in a reactive oxygen species (ROS)-dependent manner. Inhibition of mechanistic target of rapamycin (mTOR) or activation of AMP-activated protein kinase (AMPK) during the contraction-to-memory phase transition of the antiviral response increased autophagic activity and enhanced memory NK cell numbers through an Atg3-dependent mechanism...
August 18, 2015: Immunity
https://www.readbyqxmd.com/read/26183715/treatment-with-cucurbitacin-b-alone-and-in-combination-with-gefitinib-induces-cell-cycle-inhibition-and-apoptosis-via-egfr-and-jak-stat-pathway-in-human-colorectal-cancer-cell-lines
#4
A S Yar Saglam, E Alp, Z Elmazoglu, S Menevse
The epidermal growth factor receptor (EGFR) associated with signaling pathways, such as Janus kinase (JAK)/signal transducer and activator of transcription (STAT), plays an important role in colorectal cancers (CRCs). Gefitinib (Gef) is an orally active inhibitor targeting the adenosine tri phosphate-binding domain of EGFR, and cucurbitacin B (CuB) is a selective inhibitor of JAK/STAT signaling with potent antitumor activity via suppression of STAT3 phosphorylation, but the underlying mechanism is not clear...
May 2016: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/25701202/di-2-ethylhexyl-phthalate-inhibits-antral-follicle-growth-induces-atresia-and-inhibits-steroid-hormone-production-in-cultured-mouse-antral-follicles
#5
Patrick R Hannon, Katherine E Brannick, Wei Wang, Rupesh K Gupta, Jodi A Flaws
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...
April 1, 2015: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/25275009/activation-of-mitochondrial-protease-oma1-by-bax-and-bak-promotes-cytochrome-c-release-during-apoptosis
#6
Xian Jiang, Hui Jiang, Zhirong Shen, Xiaodong Wang
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...
October 14, 2014: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/24788683/increase-of-zinc-finger-protein-179-in-response-to-ccaat-enhancer-binding-protein-delta-conferring-an-antiapoptotic-effect-in-astrocytes-of-alzheimer-s-disease
#7
Shao-Ming Wang, Yi-Chao Lee, Chiung-Yuan Ko, Ming-Derg Lai, Ding-Yen Lin, Ping-Chieh Pao, Jhih-Ying Chi, Yu-Wei Hsiao, Tsung-Lin Liu, Ju-Ming Wang
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...
February 2015: Molecular Neurobiology
https://www.readbyqxmd.com/read/24637330/airway-mesenchymal-cell-death-by-mevalonate-cascade-inhibition-integration-of-autophagy-unfolded-protein-response-and-apoptosis-focusing-on-bcl2-family-proteins
#8
Saeid Ghavami, Pawan Sharma, Behzad Yeganeh, Oluwaseun O Ojo, Aruni Jha, Mark M Mutawe, Hessam H Kashani, Marek J Los, Thomas Klonisch, Helmut Unruh, Andrew J Halayko
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...
July 2014: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/24140513/toll-like-receptor-3-plays-a-role-in-myocardial-infarction-and-ischemia-reperfusion-injury
#9
Chen Lu, Danyang Ren, Xiaohui Wang, Tuanzhu Ha, Li Liu, Eric J Lee, Jing Hu, John Kalbfleisch, Xiang Gao, Race Kao, David Williams, Chuanfu Li
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...
January 2014: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/23589839/myc-induced-ampk-phospho-p53-pathway-activates-bak-to-sensitize-mitochondrial-apoptosis
#10
Anni I Nieminen, Vilja M Eskelinen, Heidi M Haikala, Topi A Tervonen, Yan Yan, Johanna I Partanen, Juha Klefström
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...
May 14, 2013: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/23480852/bak-activation-is-necessary-and-sufficient-to-drive-ceramide-synthase-dependent-ceramide-accumulation-following-inhibition-of-bcl2-like-proteins
#11
Levi J Beverly, Lauren A Howell, Maria Hernandez-Corbacho, Lavona Casson, Jerry E Chipuk, Leah J Siskind
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...
May 15, 2013: Biochemical Journal
https://www.readbyqxmd.com/read/23436224/diversification-and-senescence-of-foxp3-regulatory-t-cells-during-experimental-autoimmune-encephalomyelitis
#12
Sharyn Tauro, Phuong Nguyen, Bofeng Li, Terrence L Geiger
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...
May 2013: European Journal of Immunology
https://www.readbyqxmd.com/read/22197342/bcl2-at-the-endoplasmic-reticulum-protects-against-a-bax-bak-independent-paraptosis-like-cell-death-pathway-initiated-via-p20bap31
#13
Hannah M Heath-Engel, Bing Wang, Gordon C Shore
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...
February 2012: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/21940310/cyclopamine-blocked-the-growth-of-colorectal-cancer-sw116-cells-by-modulating-some-target-genes-of-gli1-in-vitro
#14
Jian-Ye Wu, Xuan-Fu Xu, Ling Xu, Pei-Qin Niu, Feng Wang, Guo-Yong Hu, Xing-Peng Wang, Chuan-Yong Guo
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...
September 2011: Hepato-gastroenterology
https://www.readbyqxmd.com/read/21074850/periodontal-pathogen-aggregatibacter-actinomycetemcomitans-lps-induces-mitochondria-dependent-apoptosis-in-human-placental-trophoblasts
#15
Y Li, Y Shibata, L Zhang, N Kuboyama, Y Abiko
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...
January 2011: Placenta
https://www.readbyqxmd.com/read/20885444/single-point-mutations-of-a-lysine-residue-change-function-of-bax-and-bcl-xl-expressed-in-bax-and-bak-less-mouse-embryonic-fibroblasts-novel-insights-into-the-molecular-mechanisms-of-bax-induced-apoptosis
#16
I Szabò, M Soddemann, L Leanza, M Zoratti, E Gulbins
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...
March 2011: Cell Death and Differentiation
https://www.readbyqxmd.com/read/20386468/il-7-enhances-survival-of-human-cd56bright-nk-cells
#17
Annie Michaud, R'Kia Dardari, Emily Charrier, Paulo Cordeiro, Sabine Herblot, Michel Duval
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...
May 2010: Journal of Immunotherapy
https://www.readbyqxmd.com/read/19632297/no-association-between-the-bcl2-interacting-killer-bik-gene-and-schizophrenia
#18
Kazutaka Ohi, Ryota Hashimoto, Yuka Yasuda, Hidenaga Yamamori, Hiroaki Hori, Osamu Saitoh, Masahiko Tatsumi, Masatoshi Takeda, Nakao Iwata, Norio Ozaki, Kunitoshi Kamijima, Hiroshi Kunugi
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...
September 29, 2009: Neuroscience Letters
https://www.readbyqxmd.com/read/19390557/different-forms-of-cell-death-induced-by-putative-bcl2-inhibitors
#19
M Vogler, K Weber, D Dinsdale, I Schmitz, K Schulze-Osthoff, M J S Dyer, G M Cohen
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...
July 2009: Cell Death and Differentiation
https://www.readbyqxmd.com/read/18218589/-functional-mrna-expression-analysis-and-classification-of-colonic-biopsy-samples-using-overall-cdna-microarray-technique
#20
Orsolya Galamb, Ferenc Sipos, Elek Dinya, Sándor Spisák, Aron Somorácz, Béla Molnár, Zsolt Tulassay
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)...
February 3, 2008: Orvosi Hetilap
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