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Caspase 11

Chunhua Wang, Dongmei Lin, Quan Chen, Shuqian Lin, Songsheng Shi, Chunmei Chen
The Ganoderma lucidum ( G. lucidum ) mushroom is one of the most extensively studied functional foods, known for its numerous health benefits, including the inhibition of tumor cell growth. The present study assessed the anti-proliferative and pro-apoptotic activity of a novel G. lucidum polysaccharide peptide (GL-PP) in human glioma U251 cells, which was purified from grass-cultured G. lucidum . GL-PP is a glycopeptide with an average molecular weight of 42,635 Da and a polysaccharide-to-peptide ratio of 88...
April 2018: Oncology Letters
H Amor, A Zeyad, Y Alkhaled, M Laqqan, A Saad, H Ben Ali, M E Hammadeh
The aim of this study was to assess the stability of nuclear and mitochondrial DNA (n-DNA and mt-DNA) of spermatozoa under freeze-thawing and to find out the correlation between them and their association with standard sperm parameters. Forty-three semen samples were collected from fertile (G.1; n = 29) and sub-fertile (G.2; n = 14). N-DNA fragmentation was determined by TUNEL assay and mt-DNA using caspase 3 staining. Each semen sample was frozen at -196°C by the programmed freezer. Freeze-thawing decrease vitality, total motility and membrane integrity from (43...
March 12, 2018: Andrologia
Serena Ceriotti, Anna Lange Consiglio, Lavinia Casati, Fausto Cremonesi, Valeria Sibilia, Francesco Ferrucci
Increasing evidence suggests a role for ghrelin in the control of articular inflammatory diseases like osteoarthritis (OA). In the present study we examined the ability of ghrelin to counteract LPS-induced necrosis and apoptosis of chondrocytes and the involvement of GH secretagogue receptor (GHS-R)1a in the protective action of ghrelin. The effects of ghrelin (10-7 -10-11  mol/L) on equine primary cultured chondrocytes viability and necrosis in basal conditions and under LPS treatment (100 ng/ml) were detected by using both acridine orange/propidium iodide staining and annexin-5/propidium iodide staining...
March 8, 2018: Peptides
Lan H Chu, Mohanalaxmi Indramohan, Rojo A Ratsimandresy, Anu Gangopadhyay, Emily P Morris, Denise M Monack, Andrea Dorfleutner, Christian Stehlik
Lipopolysaccharide (LPS) of Gram-negative bacteria can elicit a strong immune response. Although extracellular LPS is sensed by TLR4 at the cell surface and triggers a transcriptional response, cytosolic LPS binds and activates non-canonical inflammasome caspases, resulting in pyroptotic cell death, as well as canonical NLRP3 inflammasome-dependent cytokine release. Contrary to the highly regulated multiprotein platform required for caspase-1 activation in the canonical inflammasomes, the non-canonical mouse caspase-11 and the orthologous human caspase-4 function simultaneously as innate sensors and effectors, and their regulation is unclear...
March 8, 2018: Nature Communications
Shasha Liu, Bingrong Liu
BACKGROUND Colorectal cancer (CRC) is the third most common cancer worldwide, making it is a serious threat to human health. It is imperative to develop new therapeutics to improve the CRC treatment efficiency. The aim of this study was to investigate the role of NPRL2 in improving sensitivity to CPT-11 in colon cancer cells. MATERIAL AND METHODS NPRL2 overexpression was established by transfecting the recombinant lentivirus-encoding NPRL2 gene into HCT116 colon cancer cells. Cell proliferation was identified using Cell Counting Kit-8 (CCK8) assay...
March 9, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Asha Lekshmi, Shankara Narayanan Varadarajan, Santhik Subhasingh Lupitha, Mydhily Nair, Aneesh Chandrasekharan, T R Santhoshkumar
Recent cell biology studies reveal that a cell can die through multiple pathways via distinct signaling mechanisms. Among these, apoptosis and necrosis are two distinct cell death pathways, and their detection and discrimination is vital in the drug discovery process and in understanding diverse biological processes. Although sensitive assays for apoptosis and necrosis are available, it is extremely difficult to adapt any of these methods to discriminate apoptosis-inducing stimuli from necrosis-inducing stimuli because of the acquisition of secondary necrosis by apoptotic cells when they are not phagocytosed...
February 21, 2018: Current Protocols in Toxicology
Keigo Okada, Ayako Nogami, Shinya Ishida, Hiroki Akiyama, Cheng Chen, Yoshihiro Umezawa, Osamu Miura
FLT3-ITD is the most frequent tyrosine kinase mutation in acute myeloid leukemia (AML) associated with poor prognosis. We previously reported that activation of STAT5 confers resistance to PI3K/Akt inhibitors on the FLT3-ITD-positive AML cell line MV4-11 and 32D cells driven by FLT3-ITD (32D/ITD) but not by FLT3 mutated in the tyrosine kinase domain (32D/TKD). Here, we report the involvement of Pim kinases expressed through STAT5 activation in acquisition of this resistance. The specific pan-Pim kinase inhibitor AZD1208 as well as PIM447 in combination with the PI3K inhibitor GDC-0941 or the Akt inhibitor MK-2206 cooperatively downregulated the mTORC1/4EBP1 pathway, formation of the eIF4E/eIF4G complex, and Mcl-1 expression leading to activation of Bak and Bax to induce caspase-dependent apoptosis synergistically in these cells...
February 6, 2018: Oncotarget
Xiaoyang Li, Yuri K Peterson, Elizabeth S Inks, Richard Himes, Jiaying Li, Yingjie Zhang, Xiujie Kong, C James Chou
Previously we designed and synthesized a series of o-aminobenzamide-based HDAC inhibitors, among which the representative compound 11a exhibited potent inhibitory activity against class I HDACs. In this study, we report the development of more potent hydrazide-based class I selective HDAC inhibitors using 11a as a lead. Representative compound 13b showed a mixed, slow, and tight binding inhibition mechanism for HDAC1, 2 and 3. The most potent compound 13e exhibited low nano-molar IC50s toward HDAC1, 2 and 3, and could down-regulate HDAC6 in acute myeloid leukemia MV4-11 cells...
March 2, 2018: Journal of Medicinal Chemistry
Biao Tang, Chang-Qing Deng
Pyroptosis is a form of inflammatory programmed cell death activated by caspase-1 and caspase-4/5/11, and involves in the pathogenesis of infectious diseases and nervous system diseases. Pyroptosis is mediated by canonical inflammasome pathway and non-canonical inflammasome pathway. The canonical inflammasome pathway is activated in stroke and aggravates brain injury. Inhibition of inflammasome, caspase-1, IL-1β and IL-18 ameliorates brain injury. These studies indicate that canonical inflammasome pathway contributes to post-stroke brain injury, therefore, pyroptosis has become a potential therapeutic target for preventing excessive cell death during stroke...
February 25, 2018: Sheng Li Xue Bao: [Acta Physiologica Sinica]
Naris Nilubol, ZiQiang Yuan, Giulio F Paciotti, Lawrence Tamarkin, Carmen Sanchez, Kelli Gaskins, Esther M Freedman, Shugeng Cao, Jielu Zhao, David G I Kingston, Steven K Libutti, Electron Kebebew
Background: The advantages of nanomedicines include preferential delivery of the payload directly to tumor tissues. CYT-21625 is the novel, first-in-class gold nanomedicine designed to target tumor vasculature and cancer cells by specifically delivering recombinant human tumor necrosis factor alpha (rhTNF) and a paclitaxel prodrug. Methods: We analyzed TNF receptor expression in publicly available gene expression profiling data and in thyroid tissue samples. Mice with metastatic FTC-133 and 8505C xenografts and the MEN1 conditional knock-out mice were treated weekly with CYT-21625 and gold nanoparticles with rhTNF only (CYT-6091); controls included mice treated with either paclitaxel or saline...
February 22, 2018: Journal of the National Cancer Institute
Hani Oweira, Imad Lahdou, Volker Daniel, Jan Schmidt, Arianeb Mehrabi, Mahmoud Sadeghi
BACKGROUND We evaluated whether effluent parameters prior to reperfusion correlate with post-transplant outcomes in liver transplant recipients. MATERIAL AND METHODS Concentrations of high mobility group box 1 protein (HMGB1), uncleaved cytokeratin-18 (M65), caspase-cleaved cytokeratin 18 fragment (M30), alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), and alkaline phosphatase (ALP) were measured in effluent samples from 53 adult liver recipients (42 survived for 1 year and 11 did not survive)...
February 23, 2018: Annals of Transplantation: Quarterly of the Polish Transplantation Society
Mehtap Danismazoglu, Remziye Nalcacioglu, Hacer Muratoglu, Zihni Demirbag
Entomopoxviruses are an important group of viruses infecting only insects. They belong to Poxviridae which infect both invertebrates and vertebrates, including humans. Protein kinases are known to have roles at virus morphogenesis, host selectivity, the regulation of cell division and apoptosis in some vertebrate poxviruses. In this study, 2 protein kinases (PKs) (AMV153 and AMV197) of Amsacta moorei entomopoxvirus (AMEV) were investigated for the interactions among 230 viral proteins using yeast two-hybrid system (Y2H)...
February 19, 2018: Virus Research
Xinfeng Fan, Penglong Wang, Yaogui Sun, Junbing Jiang, Haiyuan Du, Zhirui Wang, Zhibian Duan, Haimin Lei, Hongquan Li
The aim of the present study was to investigate the effects of an oleanolic acid derivative, a novel antitumor drug, on the growth of SMMC-7721 human hepatocellular carcinoma cells and the underlying mechanism. An MTT assay was performed to determine the cytotoxicity of the oleanolic acid derivative. Cell membrane integrity was assessed using fluorescence microscopy to assess the uptake of annexin V-FITC/propidium iodide (PI). Western blotting was used to detect the apoptosis-associated proteins B cell lymphoma-2 (Bcl-2), Bax, caspase-9 and caspase-3...
March 2018: Oncology Letters
Lan Gu, Ran Meng, Yiting Tang, Kai Zhao, Fang Liang, Rui Zhang, Qianqian Xue, Fangping Chen, Xianzhong Xiao, Huadong Wang, Haichao Wang, Timothy R Billiar, Ben Lu
Outer membrane vesicles (OMVs), released by variety of bacteria, are membrane-enclosed entities enriched in microbial components, toxins and virulent factors. OMVs could deliver lipopolysaccharide (LPS) into the cytosol of host cells and subsequently activate caspase-11, which critically orchestrates immune responses and mediates septic shock. Though it is known that caspase-11 is activated by intracellular LPS, how OMVs deliver LPS into the cytosol remains largely unknown. Here we show that the activation of toll like receptor 4 (TLR4), a LPS receptor on the cytoplasmic membrane, licenses macrophages to transport LPS from OMVs into the cytosol through TIR domain-containing adaptor-inducing interferon-β (TRIF)...
February 16, 2018: Shock
José Carlos Santos, Mathias S Dick, Brice Lagrange, Daniel Degrandi, Klaus Pfeffer, Masahiro Yamamoto, Etienne Meunier, Pawel Pelczar, Thomas Henry, Petr Broz
Pathogenic and commensal Gram-negative bacteria produce and release outer membrane vesicles (OMVs), which present several surface antigens and play an important role for bacterial pathogenesis. OMVs also modulate the host immune system, which makes them attractive as vaccine candidates. At the cellular level, OMVs are internalized by macrophages and deliver lipopolysaccharide (LPS) into the host cytosol, thus activating the caspase-11 non-canonical inflammasome. Here, we show that OMV-induced inflammasome activation requires TLR4-TRIF signaling, the production of type I interferons, and the action of guanylate-binding proteins (GBPs), both in macrophages and in vivo Mechanistically, we find that isoprenylated GBPs associate with the surface of OMVs or with transfected LPS, indicating that the key factor that determines GBP recruitment to the Gram-negative bacterial outer membranes is LPS itself...
February 19, 2018: EMBO Journal
Wei Liu, Yuhua Chen, Jiao Meng, Minfei Wu, Fangfang Bi, Cuicui Chang, Hua Li, Liangjun Zhang
BACKGROUND: Traumatic brain injury (TBI) is a critical public health and socioeconomic problem throughout the world. Inflammation-induced secondary injury is one of the vital pathogenic parameters of TBI. Molecular signaling cascades of pyroptosis, a specific type of cellular necrosis, are key drivers of TBI-induced inflammation. METHODS: In this study, mice with genetically ablated caspase-1 (caspase-1-/- ) were subjected to controlled cortical impact injury in vivo, and primary neuron deficient in caspase-1 through siRNA knockdown and pharmacologic inhibition was stimulated by mechanical scratch, equiaxial stretch, and LPS/ATP in vitro...
February 19, 2018: Journal of Neuroinflammation
Cynthia Lebeaupin, Déborah Vallée, Déborah Rousseau, Stéphanie Patouraux, Stéphanie Bonnafous, Gilbert Adam, Frederic Luciano, Carmelo Luci, Rodolphe Anty, Antonio Iannelli, Sandrine Marchetti, Guido Kroemer, Sandra Lacas-Gervais, Albert Tran, Philippe Gual, Béatrice Bailly-Maitre
Endoplasmic reticulum (ER) stress is activated in non-alcoholic fatty liver disease (NAFLD), raising the possibility that ER stress-dependent metabolic dysfunction, inflammation and cell death underlie the transition from steatosis to steatohepatitis (NASH). Bax inhibitor-1 (BI-1), a negative regulator of the ER stress sensor IRE1α, has yet to be explored in NAFLD as a hepatoprotective agent. We hypothesized that the genetic ablation of BI-1 would render the liver vulnerable to NASH due to unrestrained IRE1α signaling...
February 19, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Yiwei Shen, Zhouliang Sun, Peiying Shi, Gang Wang, Youjia Wu, Shaoguang Li, Yanjie Zheng, Liying Huang, Liqing Lin, Xinhua Lin, Hong Yao
ETHNOPHARMACOLOGICAL RELEVANCE: Bidens pilosa L, belonging to the family of Acanthaceae, has been used as an anticancer medicine in folk in China. In our preliminary experiments, the petroleum ether extract from B. pilosa showed good cytotoxic activity to human lung cancer A549 cell. However, to date, it's lack of the further study on antitumor effect, mechanism and active substances composition of the petroleum ether extract of B. pilosa. AIM OF THE STUDY: The study aimed to evaluate the anti-lung cancer efficacy of the petroleum ether extract from B...
February 15, 2018: Journal of Ethnopharmacology
Sonu Kumar, Piotr Cieplak
Posttranslational modifications that involve either reversible covalent modification of proteins or irreversible proteolysis are central to the regulation of key cellular mechanisms, including apoptosis, cell-cycle regulation and signal transduction. There is mounting evidence suggesting cross-talk between proteases and kinases. For instance: caspases, a class of proteases involved in programmed cell death-apoptosis, cleave a large set of various types of proteins. Simultaneously, kinases restrict caspase activity by phosphorylating their protein substrates in the vicinity of cleavage site...
February 16, 2018: Apoptosis: An International Journal on Programmed Cell Death
Katarzyna Knapczyk-Stwora, Malgorzata Grzesiak, Renata E Ciereszko, Elzbieta Czaja, Marek Koziorowski, Maria Slomczynska
The objective of the study was to examine the effects of androgen and estrogen agonists or antagonists on the follicle formation, ovarian cell proliferation and apoptosis as well as plasma steroid concentration in neonatal pigs. Piglets were injected with testosterone propionate (TP, 20 mg/kg bw), flutamide (FLU, 50 mg/kg bw), 4-tert-octylphenol (OP, 100 mg/kg bw), ICI 182,780 (ICI, 400 μg/kg bw), methoxychlor (MXC, 100 mg/kg bw) or corn oil (CTR, controls) between postnatal Days 1 and 10 (n = 4/group). Heart blood was collected and ovaries were excised from the 11-day-old piglets...
February 10, 2018: Theriogenology
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