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https://www.readbyqxmd.com/read/29142064/the-resurrection-of-the-piddosome-emerging-roles-in-the-dna-damage-response-and-centrosome-surveillance
#1
REVIEW
Valentina Sladky, Fabian Schuler, Luca L Fava, Andreas Villunger
The PIDDosome is often used as the alias for a multi-protein complex that includes the p53-induced death domain protein 1 (PIDD1), the bipartite linker protein CRADD (also known as RAIDD) and the pro-form of an endopeptidase belonging to the caspase family, i.e. caspase-2. Yet, PIDD1 variants can also interact with a number of other proteins that include RIPK1 (also known as RIP1) and IKBKG (also known as NEMO), PCNA and RFC5, as well as nucleolar components such as NPM1 or NCL. This promiscuity in protein binding is facilitated mainly by autoprocessing of the full-length protein into various fragments that contain different structural domains...
November 15, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/29131627/enhancement-of-9%C3%AE-hydroxy-4-androstene-3-17-dione-production-from-soybean-phytosterols-by-deficiency-of-a-regulated-intramembrane-proteolysis-metalloprotease-in-mycobacterium-neoaurum
#2
Liang-Bin Xiong, Wan-Ju Sun, Yong-Jun Liu, Feng-Qing Wang, Dong-Zhi Wei
Modification of the sterol catabolism pathway in mycobacteria may result in the accumulation of some valuable steroid pharmaceutical intermediates, such as 9α-hydroxy-4-androstene-3,17-dione (9-OHAD). In previous work, the SigD was identified as a negative factor of the 9-OHAD production in M. neoaurum. Here, the deficiency of rip1 putatively coding for a regulated intramembrane proteolysis metalloprotease (Rip1), which could cleave the negative regulator of SigD (anti-SigD), enhanced the transcription of some key genes (choM1, kshA and hsd4A) in the sterol catabolic pathway...
November 13, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/29116428/bromoethylindole-bei-9-redirects-nf-%C3%AE%C2%BAb-signaling-induced-by-camptothecin-and-tnf%C3%AE-to-promote-cell-death-in-colon-cancer-cells
#3
Rupak Chowdhury, Dominique Gales, Paloma Valenzuela, Sonni Miller, Teshome Yehualaeshet, Upender Manne, Giulio Francia, Temesgen Samuel
Chemotherapeutic regimens containing camptothecin (CPT), 5-fluorouracil, and oxaliplatin are used to treat advanced colorectal cancer. We previously reported that an indole derivative, 3-(2-bromoethyl)indole (BEI-9), inhibited the proliferation of colon cancer cells and suppressed NF-κB activation. Here, we show that a combination of BEI-9 with either CPT or tumor necrosis factor alpha (TNFα) enhances cell death. Using colorectal cancer cells, we examined the activation of NF-κB by drugs, the potential of BEI-9 for inhibiting drug-induced NF-κB activation, and the enhancement of cell death by combination treatments...
November 8, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/29075784/lippia-origanoides-extract-induces-cell-cycle-arrest-and-apoptosis-and-suppresses-nf-%C3%AE%C2%BAb-signaling-in-triple-negative-breast-cancer-cells
#4
Vishak Raman, Jorge Luis Fuentes Lorenzo, Elena E Stashenko, Morris Levy, Maria M Levy, Ignacio G Camarillo
Treatments targeting hormone receptors typically fail to provide a positive clinical outcome against triple-negative breast cancers (TNBC), which lack expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (Her2/neu). Towards identifying viable treatments for aggressive breast cancer, we have tested an extract of the tropical plant Lippia origanoides (LOE) on TNBC and normal cells lines to uncover its potential anticancer effects. Treatment with LOE reduced TNBC cell viability in a dose-dependent manner to a greater extent than in normal mammary epithelial MCF10A cells...
December 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29021293/ppar%C3%AE-ligand-induced-annexin-a1-expression-determines-chemotherapy-response-via-deubiquitination-of-death-domain-kinase-rip-in-triple-negative-breast-cancers
#5
Luxi Chen, Yi Yuan, Shreya Kar, Madhu M Kanchi, Suruchi Arora, Ji E Kim, Pei F Koh, Einas Yousef, Ramar P Samy, Muthu K Shanmugam, Tuan Z Tan, Sung W Shin, Frank Arfuso, Han M Shen, Henry Yang, Boon C Goh, Joo I Park, Louis Gaboury, Peter E Lobie, Gautam Sethi, Lina H K Lim, Alan P Kumar
Metastatic breast cancer is still incurable so far; new specifically targeted and more effective therapies for triple-negative breast cancer (TNBC) are required in the clinic. In this study, our clinical data have established that basal and claudin-low subtypes of breast cancer (TNBC types) express significantly higher levels of Annexin A1 (ANXA1) with poor survival outcomes. Using human cancer cell lines that model the TNBC subtype, we observed a strong positive correlation between expression of ANXA1 and PPARγ...
August 15, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28993192/up-regulation-of-rip3-alleviates-cervical-cancer-progression-through-inducing-necroptosis
#6
Dong-Li Zhang, Gui-Xia Sun, Jun Tian, Hong-Xia Zhang
Receptor-interacting protein kinase-3 (RIP3 or RIPK3) is an important part of the cellular machinery, executing programmed necroptosis. However, the biological role and clinical significance of RIP3 in cervical cancer remains to be further elucidated. Here, we reported that RIP3 was expressed lowly in cervical cancer cell lines and clinical cervical tumor samples, along with the reduction of receptor-interacting protein 1 (RIP1) and p-mixed lineage kinase domain-like protein (MLKL). Further, we found that over-expressing RIP3 suppressed the proliferation and tumorigenicity of cervical cancer cells both in vitro and in vivo...
October 6, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28987363/extract-from-mulberry-morus-australis-leaf-decelerate-acetaminophen-induced-hepatic-inflammation-involving-downregulation-of-myeloid-differentiation-factor-88-myd88-signals
#7
Chi-Ting Horng, Zhi-Hong Liu, Yu-Ting Huang, Huei-Jane Lee, Chau-Jong Wang
Acetaminophen (APAP) induced inflammation and oxidative stress can cause cell death to induce liver damage. The antioxidative and anti-inflammatory effect of Mulberry (Morus australis) leaf extract (MLE) was shown in previous studies. In this study, we investigated the modulation of MLE on APAP induced inflammation and oxidative stress in rat liver injury or liver cancer cell (HepG2). Wistar rat was fed orally with MLE (0.5% or 1.0 %) for 1 week, and then, 900 mg/kg of APAP was injected intraperitoneally (i...
October 2017: Journal of Food and Drug Analysis
https://www.readbyqxmd.com/read/28978109/sorafenib-inhibits-therapeutic-induction-of-necroptosis-in-acute-leukemia-cells
#8
Friederike Feldmann, Barbara Schenk, Sofie Martens, Peter Vandenabeele, Simone Fulda
Induction of necroptosis has emerged as an alternative approach to trigger programmed cell death, in particular in apoptosis-resistant cancer cells. Recent evidence suggests that kinase inhibitors targeting oncogenic B-RAF can also affect Receptor-interacting serine/threonine-protein kinase (RIP)1 and RIP3. Sorafenib, a multi-targeting kinase inhibitor with activity against B-RAF, is used for the treatment of acute leukemia. In the present study, we therefore investigated whether Sorafenib interferes with therapeutic induction of necroptosis in acute leukemia...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28970360/heat-shock-protein-70-hsp70-suppresses-rip1-dependent-apoptotic-and-necroptotic-cascades
#9
Sharan R Srinivasan, Laura C Cesa, Xiaokai Li, Olivier Julien, MIn Zhuang, Hao Shao, Jooho Chung, Ivan Maillard, James A Wells, Colin Duckett, Jason E Gestwicki
Heat shock protein 70 (Hsp70) is a molecular chaperone that binds to "client" proteins and protects them from protein degradation. Hsp70 is essential for the survival of many cancer cells, but it is not yet clear which of its clients are involved. Using structurally distinct chemical inhibitors, we found that many of the well-known clients of the related chaperone, Hsp90, are not strikingly responsive to Hsp70 inhibition. Rather, Hsp70 appeared to be important for the stability of the RIP1 (RIPK1) regulators: cIAP1/2 (BIRC1 and BIRC3), XIAP, and cFLIPS/L (CFLAR)...
September 28, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28960436/hydrogen-peroxide-induces-programmed-necrosis-in-rat-nucleus-pulposus-cells-through-the-rip1-rip3-parp-aif-pathway
#10
Lei Zhao, Hui Lin, Songfeng Chen, Sheng Chen, Min Cui, Deyao Shi, Baichuan Wang, Kaige Ma, Zengwu Shao
This study aimed to systematically investigate whether programmed necrosis contributes to H2 O2 -induced nucleus pulposus (NP) cells death and to further explore the underlying mechanism involved. Rat NP cells were subjected to different concentrations of H2 O2 for various time periods. The cell viability was measured using a cell counting kit-8, and the death rate was detected by Hoechst 33258/propidium iodide staining. The programmed necrosis-related molecules receptor-interacting protein 1 (RIP1), receptor-interacting protein 3 (RIP3), poly (ADP-ribose) polymerase (PARP) and apoptosis inducing factor (AIF) were determined by real-time polymerase chain reaction and western blotting, respectively...
September 28, 2017: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/28957350/does-necroptosis-have-a-crucial-role-in-hepatic-ischemia-reperfusion-injury
#11
Waqar K Saeed, Dae Won Jun, Kiseok Jang, Yeon Ji Chae, Jai Sun Lee, Hyeon Tae Kang
BACKGROUND: Previous studies have demonstrated protective effects of anti-receptor interacting protein kinase 1 (RIP1), a key necroptosis molecule. However, it is uncertain whether necroptosis has a crucial role in hepatic IR injury. Therefore, we evaluated the role of necroptosis in hepatic IR injury. METHOD: The IR mice underwent 70% segmental IR injury induced by the clamping of the hepatic artery and portal vein for 1 hr followed by reperfusion for 4 hr. The key necroptosis molecules (RIP1, RIP3, and MLKL) and other key molecules of regulated necrosis (PGAM5 and caspase-1) were evaluated in the warm IR injury model...
2017: PloS One
https://www.readbyqxmd.com/read/28940129/the-role-of-smurf1-in-neuronal-necroptosis-after-lipopolysaccharide-induced-neuroinflammation
#12
Lifei Shao, Xiaojuan Liu, Shunxing Zhu, Chun Liu, Yilu Gao, Xide Xu
The role of inflammation in neurological disorders such as Alzheimer's disease and Parkinson's disease is gradually recognized and leads to an urgent challenge. Smad ubiquitination regulatory factor 1 (Smurf1), one member of the HECT family, is up-regulated by proinflammatory cytokines and associated with apoptosis in acute spinal cord injury. However, the function of Smurf1 through promoting neuronal necroptosis is still limited in the central nervous system (CNS). Hence, we developed a neuroinflammatory model in adult rats following lipopolysaccharide (LPS) lateral ventral injection to elaborate whether Smurf1 is involved in necroptosis in CNS injury...
September 22, 2017: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/28927431/role-of-the-sigma-1-receptor-chaperone-in-rod-and-cone-photoreceptor-degenerations-in-a-mouse-model-of-retinitis-pigmentosa
#13
Huan Yang, Yingmei Fu, Xinying Liu, Pawan K Shahi, Timur A Mavlyutov, Jun Li, Annie Yao, Steven Z-W Guo, Bikash R Pattnaik, Lian-Wang Guo
BACKGROUND: Retinitis pigmentosa (RP) is the most common inherited retinal degenerative disease yet with no effective treatment available. The sigma-1 receptor (S1R), a ligand-regulated chaperone, emerges as a potential retina-protective therapeutic target. In particular, pharmacological activation of S1R was recently shown to rescue cones in the rd10 mouse, a rod Pde6b mutant that recapitulates the RP pathology of autonomous rod degeneration followed by secondary death of cones. The mechanisms underlying the S1R protection for cones are not understood in detail...
September 19, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28923396/smac-mimetics-and-type-ii-interferon-synergistically-induce-necroptosis-in-various-cancer-cell-lines
#14
Michael John Cekay, Stefanie Roesler, Tanja Frank, Anne-Kathrin Knuth, Ines Eckhardt, Simone Fulda
Since cancer cells often evade apoptosis, induction of necroptosis as another mode of programmed cell death is considered a promising therapeutic alternative. Here, we identify a novel synergistic interaction of Smac mimetics that antagonize x-linked Inhibitor of Apoptosis (XIAP), cellular Inhibitor of Apoptosis (cIAP) 1 and 2 with interferon (IFN)γ to induce necroptosis in apoptosis-resistant cancer cells in which caspase activation is blocked. This synergism is confirmed by calculation of combination indices (CIs) and found in both solid and hematological cancer cell lines as well as for different Smac mimetics (i...
September 18, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28900035/prion-protein-is-required-for-tumor-necrosis-factor-alpha-tnf%C3%AE-triggered-nuclear-factor-kappa-b-nf-%C3%AE%C2%BAb-signaling-and-cytokine-production
#15
Gui-Ru Wu, Tian-Chen Mu, Zhen-Xing Gao, Jun Wang, Man-Sun Sy, Chao-yang Li
The expression of normal cellular prion protein (PrP) is required for the pathogenesis of prion diseases. However, the physiological functions of PrP remain ambiguous. Here, we identified PrP as being critical for tumor necrosis factor (TNF)α-triggered signaling in a human melanoma cell line, M2, and a pancreatic ductal cell adenocarcinoma cell line, BxPC-3. In M2 cells, TNFα upregulates the expression of p-I-kappa-B-kinase α/β (p-IKKα/β), p-p65, and p-JNK, but downregulates the IκBα protein, all of which are downstream signaling intermediates in the TNF receptor signaling cascade...
September 12, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28892675/alkynyl-gold-i-complex-triggers-necroptosis-via-ros-generation-in-colorectal-carcinoma-cells
#16
Inés Mármol, María Virumbrales-Muñoz, Javier Quero, Cristina Sánchez-de-Diego, Luis Fernández, Ignacio Ochoa, Elena Cerrada, Mª Jesús Rodríguez Yoldi
Given the rise of apoptosis-resistant tumors, there exist a growing interest in developing new drugs capable of inducing different types of cell death to reduce colorectal cancer-related death rates. As apoptosis and necroptosis do not share cellular machinery, necroptosis induction may have a great therapeutic potential on those apoptosis-resistant cancers, despite the inflammatory effects associated with it. We have synthesized an alkynyl gold(I) complex [Au(CC-2-NC5H4)(PTA)] whose anticancer effect was tested on the colorectal adenocarcinoma Caco-2 cell line...
November 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/28887702/necroptosis-may-be-a-novel-mechanism-for-cardiomyocyte-death-in-acute-myocarditis
#17
Fei Zhou, Xuejun Jiang, Lin Teng, Jun Yang, Jiawang Ding, Chao He
In this study, we investigated the roles of RIP1/RIP3 mediated cardiomyocyte necroptosis in CVB3-induced acute myocarditis. Serum concentrations of creatinine kinase (CK), CK-MB, and cardiac troponin I were detected using a Hitachi Automatic Biochemical Analyzer in a mouse model of acute VMC. Histological changes in cardiac tissue were observed by light microscope and expression levels of RIP1/RIP3 in the cardiac tissue were detected via Western blot and immunohistochemistry. The data showed that RIP1/RIP3 was highly expressed in cardiomyocytes in the acute VMC mouse model and that the necroptosis pathway specific blocker, Nec-1, dramatically reduced the myocardial damage by downregulating the expression of RIP1/RIP3...
September 8, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28885615/necroptosis-in-microglia-contributes-to-neuroinflammation-and-retinal-degeneration-through-tlr4-activation
#18
Zijing Huang, Tian Zhou, Xiaowei Sun, Yingfeng Zheng, Bing Cheng, Mei Li, Xialin Liu, Chang He
Inflammation has emerged to be a critical mechanism responsible for neural damage and neurodegenerative diseases. Microglia, the resident innate immune cells in retina, are implicated as principal components of the immunological insult to retinal neural cells. The involvement of microglia in retinal inflammation is complex and here we propose for the first time that necroptosis in microglia triggers neuroinflammation and exacerbates retinal neural damage and degeneration. We found microglia experienced receptor-interacting protein kinase 1 (RIP1)- and RIP3-dependent necroptosis not only in the retinal degenerative rd1 mice, but also in the acute retinal neural injury mice...
September 8, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28871172/the-cytoplasmic-nuclear-receptor-rar%C3%AE-controls-rip1-initiated-cell-death-when-ciap-activity-is-inhibited
#19
Qing Xu, Siriporn Jitkaew, Swati Choksi, Chamila Kadigamuwa, Jianhui Qu, Moran Choe, Jonathan Jang, Chengyu Liu, Zheng-Gang Liu
Tumor necrosis factor (TNF) has a critical role in diverse cellular events including inflammation, apoptosis and necroptosis through different signaling complexes. However, little is known about how the transition from inflammatory signaling to the engagement of death pathways is modulated. Here we report that the cytoplasmic retinoic acid receptor gamma (RARγ) controls receptor-interacting protein kinase 1 (RIP1)-initiated cell death when cellular inhibitor of apoptosis (cIAP) activity is blocked. Through screening a short hairpin RNA library, we found that RARγ was essential for TNF-induced RIP1-initiated apoptosis and necroptosis...
September 4, 2017: Nature Communications
https://www.readbyqxmd.com/read/28845215/ppar-%C3%AE-activation-prevents-septic-cardiac-dysfunction-via-inhibition-of-apoptosis-and-necroptosis
#20
Shiyan Peng, Junmei Xu, Wei Ruan, Suobei Li, Feng Xiao
Sepsis-induced cardiac dysfunction remains one of the major causes of death in intensive care units. Overwhelmed inflammatory response and unrestrained cell death play critical roles in sepsis-induced cardiac dysfunction. Peroxisome proliferator-activated receptor- (PPAR-) γ has been proven to be cardioprotective in sepsis. However, the mechanism of PPAR-γ-mediated cardioprotection and its relationship with inflammation and cell death are unclear. We hypothesized that activation of PPAR-γ by reducing cardiac inflammation, myocardial apoptosis, and necroptosis may prevent myocardial dysfunction in sepsis...
2017: Oxidative Medicine and Cellular Longevity
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