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https://www.readbyqxmd.com/read/29140165/improved-total-body-irradiation-survival-by-delivery-of-two-radiation-mitigators-that-target-distinct-cell-death-pathways
#1
Justin Steinman, Michael Epperly, Wen Hou, John Willis, Hong Wang, Renee Fisher, Bing Liu, Ivet Bahar, Travis McCaw, Valerian Kagan, Hulya Bayir, Jian Yu, Peter Wipf, Song Li, M Saiful Huq, Joel S Greenberger
The acute lethality of total-body irradiation (TBI) involves damage to multiple organs, including bone marrow and intestine. Ionizing radiation mitigators that are effective when delivered 24 h or later after TBI include the anti-apoptotic drug, JP4-039 and the anti-necroptotic drug, necrostatin-1. In contrast to effective delivery of JP4-039 at 24 h after TBI, necrostatin-1 is most effective when delivery is delayed until 48 h, a time that correlates with the elevation of necroptosis-inducing inflammatory cytokines and necroptosis-induced serine phosphorylation of receptor-interacting serine/threonine-protein kinase-3 (RIP3) in tissues...
November 15, 2017: Radiation Research
https://www.readbyqxmd.com/read/29055012/type-i-interferon-enhances-necroptosis-of-salmonella-typhimurium-infected-macrophages-by-impairing-antioxidative-stress-responses
#2
Nina Judith Hos, Raja Ganesan, Saray Gutiérrez, Deniz Hos, Jennifer Klimek, Zeinab Abdullah, Martin Krönke, Nirmal Robinson
Salmonella enterica serovar Typhimurium exploits the host's type I interferon (IFN-I) response to induce receptor-interacting protein (RIP) kinase-mediated necroptosis in macrophages. However, the events that drive necroptosis execution downstream of IFN-I and RIP signaling remain elusive. In this study, we demonstrate that S Typhimurium infection causes IFN-I-mediated up-regulation of the mitochondrial phosphatase Pgam5 through RIP3. Pgam5 subsequently interacts with Nrf2, which sequesters Nrf2 in the cytosol, thereby repressing the transcription of Nrf2-dependent antioxidative genes...
October 20, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/29037260/a-novel-protein-derived-from-lamprey-supraneural-body-tissue-with-efficient-cytocidal-actions-against-tumor-cells
#3
Yue Pang, Changzhi Li, Shiyue Wang, Wei Ba, Tao Yu, Guangying Pei, Dan Bi, Hongfang Liang, Xiong Pan, Ting Zhu, Meng Gou, Yinglun Han, Qingwei Li
BACKGROUND: In previous research, we found that cell secretion from the adult lamprey supraneural body tissues possesses cytocidal activity against tumor cells, but the protein with cytocidal activity was unidentified. METHODS: A novel lamprey immune protein (LIP) as defense molecule was first purified and identified in jawless vertebrates (cyclostomes) using hydroxyapatite column and Q Sepharose Fast Flow column. After LIP stimulation, morphological changes of tumor cells were analysed and measured whether in vivo or in vitro...
October 16, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/28993192/up-regulation-of-rip3-alleviates-cervical-cancer-progression-through-inducing-necroptosis
#4
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
#5
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/28983589/honokiol-triggers-receptor%C3%A2-interacting-protein-kinase-3%C3%A2-mediated-cell-death-of-neuroblastoma-cells-by-upregulating-reactive-oxygen-species
#6
Jiao Zhang, Qiuliang Liu, Longyan Shi, Pan Qin, Qi Wang
Neuroblastoma is the most common form of childhood extracranial tumor and almost half of neuroblastoma cases occur in infants under two years old. Neuroblastoma accounts for ~6‑10% of childhood cancers and 15% of cancer‑associated childhood mortality. However, an effective treatment remains to be developed. Honokiol exhibits long‑lasting central muscle relaxation, anti‑inflammatory, antibacterial, antimicrobial, antiulcer, antioxidation, antiaging and antitumor effects. Honokiol has been previously demonstrated to kill neuroblastoma cells, however, the underlying mechanism of action remains unclear...
December 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28981598/mixed-lineage-kinase-domain-like-protein-induces-rgc-5-necroptosis-following-elevated-hydrostatic-pressure
#7
Lvshuang Liao, Lei Shang, Na Li, Shuchao Wang, Mi Wang, Yanxia Huang, Dan Chen, Jufang Huang, Kun Xiong
Receptor-interacting protein 3 (RIP3) is an essential component of the necroptosis signaling pathway. Phosphorylation of its downstream target, mixed lineage kinase domain-like protein (MLKL), has been proposed to induce necroptosis by initiating Ca2+ influx. Our previous studies have shown that RGC-5 retinal ganglion cells undergo RIP3-mediated necroptosis following elevated hydrostatic pressure (EHP). However, the molecular mechanism underlying necroptosis induction downstream of RIP3 is still not well understood...
October 1, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/28981102/regulation-of-rip3-by-the-transcription-factor-sp1-and-the-epigenetic-regulator-uhrf1-modulates-cancer-cell-necroptosis
#8
Chengkui Yang, Jun Li, Lu Yu, Zili Zhang, Feng Xu, Lang Jiang, Xiuxia Zhou, Sudan He
Receptor-interacting kinase-3 (RIP3) is a key regulator of necroptosis. It has been shown that the expression of RIP3 is silenced in most cancer cells and tissues due to genomic methylation. However, the regulatory mechanisms controlling RIP3 expression in cancer cells have not been fully elucidated. Here, we report that Sp1, a well-characterized zinc-finger transcription factor, directly regulates RIP3 expression in cancer cells. Knockdown of endogenous Sp1 significantly decreases the transcription of Rip3, thereby further inhibiting necroptosis...
October 5, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28978109/sorafenib-inhibits-therapeutic-induction-of-necroptosis-in-acute-leukemia-cells
#9
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/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/28927431/role-of-the-sigma-1-receptor-chaperone-in-rod-and-cone-photoreceptor-degenerations-in-a-mouse-model-of-retinitis-pigmentosa
#12
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
#13
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/28887702/necroptosis-may-be-a-novel-mechanism-for-cardiomyocyte-death-in-acute-myocarditis
#14
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
#15
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/28863321/the-role-of-necroptosis-in-status-epilepticus-induced-brain-injury-in-juvenile-rats
#16
Qianyun Cai, Jing Gan, Rong Luo, Yi Qu, Shiping Li, Chaomin Wan, Dezhi Mu
PURPOSE: To study the role of necroptosis in status epilepticus (SE)-induced injury in the developing brain and the possible associations of necroptosis with epileptogenesis and cognitive dysfunction. METHODS: The lithium-pilocarpine epilepsy model was reproduced in male rats at postnatal day 25. Propidium iodide (PI) staining was used to detect cell death after SE. Transmission electron microscopy (TEM) was performed to observe morphological changes in injured neurons...
October 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/28845215/ppar-%C3%AE-activation-prevents-septic-cardiac-dysfunction-via-inhibition-of-apoptosis-and-necroptosis
#17
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
https://www.readbyqxmd.com/read/28844856/rip3-and-pmlkl-promote-necroptosis-induced-inflammation-and-alter-membrane-permeability-in-intestinal-epithelial-cells
#18
Anna Negroni, Eleonora Colantoni, Maria Pierdomenico, Francesca Palone, Manuela Costanzo, Salvatore Oliva, Antonio Tiberti, Salvatore Cucchiara, Laura Stronati
BACKGROUND: Necroptosis is an inflammatory form of programmed cell death requiring receptor-interacting protein kinase 3 (RIP3) and mixed lineage kinase domain-like protein (MLKL). AIMS: The aim of this study is to examine in depth in vitro and ex vivo the contribution of necroptosis to intestinal inflammation. METHODS: In vitro: we used an intestinal cell line, HCT116RIP3, produced in our laboratory and overexpressing RIP3. Ex vivo: intestinal mucosal biopsies were taken from patients with inflammatory bowel disease (IBD) (20 with Crohn's disease; 20 with ulcerative colitis) and from 20 controls...
August 10, 2017: Digestive and Liver Disease
https://www.readbyqxmd.com/read/28816233/shikonin-induces-glioma-cell-necroptosis-in-vitro-by-ros-overproduction-and-promoting-rip1-rip3-necrosome-formation
#19
Bin Lu, Xu Gong, Zong-Qi Wang, Ye Ding, Chen Wang, Tian-Fei Luo, Mei-Hua Piao, Fan-Kai Meng, Guang-Fan Chi, Yi-Nan Luo, Peng-Fei Ge
Necroptosis is a type of programmed necrosis regulated by receptor interacting protein kinase 1 (RIP1) and RIP3. Necroptosis is found to be accompanied by an overproduction of reactive oxygen species (ROS), but the role of ROS in regulation of necroptosis remains elusive. In this study, we investigated how shikonin, a necroptosis inducer for cancer cells, regulated the signaling leading to necroptosis in glinoma cells in vitro. Treatment with shikonin (2-10 μmol/L) dose-dependently triggered necrosis and induced overproduction of intracellular ROS in rat C6 and human SHG-44, U87 and U251 glioma cell lines...
November 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28770700/detection-of-necroptosis-in-ligand-mediated-and-hypoxia-induced-injury-of-hepatocytes-using-a-novel-optic-probe-detecting-receptor-interacting-protein-rip-1-rip3-binding
#20
Sanae Haga, Akira Kanno, Takeaki Ozawa, Naoki Morita, Mami Asano, Michitaka Ozaki
Liver injury is often observed in various pathological conditions including posthepatectomy state and cancer chemotherapy. It occurs mainly as a consequence of the combined necrotic and apoptotic types of cell death. In order to study liver/hepatocyte injury by necrotic type of cell death, we studied signal-regulated necrosis (necroptosis) by newly developing an optic probe detecting receptor-interacting protein (RIP)1/RIP3 binding, an essential process for necroptosis induction. In the mouse hepatocyte cell line, TIB-73 cells, TNF-a/cycloheximide (T/C) induced RIP1/3 binding only when caspase activity was suppressed by z-VAD-fmk (zVAD), a caspase-specific inhibitor...
July 21, 2017: Oncology Research
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