scholarly journals Curcumin modulates multiple cell death, matrix metalloproteinase activation and cardiac protein release in susceptible and resistant Plasmodium berghei-infected mice

2022 ◽  
Vol 146 ◽  
pp. 112454
Author(s):  
John O. Olanlokun ◽  
Wisdom Oshireku Abiodun ◽  
Oluwakemi Ebenezer ◽  
Neil A. Koorbanally ◽  
Olufunso Olabode Olorunsogo
Keyword(s):  
Cell Death ◽  
Matrix Metalloproteinase ◽  
Plasmodium Berghei ◽  
Protein Release ◽  
Multiple Cell

Targeting multiple cell death pathways extends the shelf life and preserves the function of human and mouse neutrophils for transfusion

2021 ◽  
Vol 13 (604) ◽  
pp. eabb1069
Author(s):  
Yuping Fan ◽  
Yan Teng ◽  
Fabien Loison ◽  
Aiming Pang ◽  
Anongnard Kasorn ◽  
...  
Keyword(s):  
Cell Death ◽  
Shelf Life ◽  
Ex Vivo ◽  
Combined Treatment ◽  
Bacterial Killing ◽  
Immunodeficient Mice ◽  
Cell Death Pathways ◽  
Multiple Cell ◽  
Human And Mouse

Clinical outcomes from granulocyte transfusion (GTX) are disadvantaged by the short shelf life and compromised function of donor neutrophils. Spontaneous neutrophil death is heterogeneous and mediated by multiple pathways. Leveraging mechanistic knowledge and pharmacological screening, we identified a combined treatment, caspases–lysosomal membrane permeabilization–oxidant–necroptosis inhibition plus granulocyte colony-stimulating factor (CLON-G), which altered neutrophil fate by simultaneously targeting multiple cell death pathways. CLON-G prolonged human and mouse neutrophil half-life in vitro from less than 1 day to greater than 5 days. CLON-G–treated aged neutrophils had equivalent morphology and function to fresh neutrophils, with no impairment to critical effector functions including phagocytosis, bacterial killing, chemotaxis, and reactive oxygen species production. Transfusion with stored CLON-G–treated 3-day-old neutrophils enhanced host defenses, alleviated infection-induced tissue damage, and prolonged survival as effectively as transfusion with fresh neutrophils in a clinically relevant murine GTX model of neutropenia-related bacterial pneumonia and systemic candidiasis. Last, CLON-G treatment prolonged the shelf life and preserved the function of apheresis-collected human GTX products both ex vivo and in vivo in immunodeficient mice. Thus, CLON-G treatment represents an effective and applicable clinical procedure for the storage and application of neutrophils in transfusion medicine, providing a therapeutic strategy for improving GTX efficacy.

scholarly journals TB-4 Antitumor effects of a novel curcumin derivative curcumin monoglucuronide on glioblastoma cells in vitro and in vivo

2021 ◽  
Vol 3 (Supplement_6) ◽  
pp. vi6-vi6
Author(s):  
Takashi Fujii ◽  
Shun Yamamuro ◽  
Masamichi Takahashi ◽  
Akihide Kondo ◽  
Yoshitaka Narita ◽  
...  
Keyword(s):  
Cell Death ◽  
Water Soluble ◽  
Dependent Manner ◽  
Antitumor Effects ◽  
Multiple Cell ◽  
Human Gbm ◽  
Dose Dependent ◽  
Novel Therapeutic

Abstract The therapeutic outcome of glioblastomas (GBMs) is still very poor. Therefore, invention of novel therapeutic methods against GBM cases is considered urgent. The antitumor effects of naturally-derived compounds are attracting attention recently, and therapeutic efficacy of curcumin, a plant-derived compound previously used for multiple purpose, has been indicated in many cancer systems; however, clinical application of curcumin is considered difficult because of its poor bioavailability (under 1 %). Curcumin monoglucuronide (CMG), a water-soluble prodrug of curcumin recently developed for overcoming this weakness, has been demonstrated excellent antitumor effects for several malignancies in vitro and in vivo; therefore, we investigated the effects of CMG against GBM cells. CMG induced cell death of human GBM cells lines (T98G, U251MG, and U87MG) by dose dependent manner by triggering multiple forms of cell death such as apoptosis and perthanatos. Immunoblotting of CMG-treated GBM cell lysates demonstrated activation of multiple cell death signaling. Furthermore, immunodeficiency mice harboring intracerebral U87MG cell xenografts systemically treated by CMG showed significantly prolonged survival compared with control mice. These results suggest CMG would be a novel therapeutic agent against GBM cases.

scholarly journals TAK1 regulates caspase 8 activation and necroptotic signaling via multiple cell death checkpoints

2016 ◽  
Vol 7 (9) ◽  
pp. e2381-e2381 ◽  
Author(s):  
Xiaoyun Guo ◽  
Haifeng Yin ◽  
Yi Chen ◽  
Lei Li ◽  
Jing Li ◽  
...  
Keyword(s):  
Cell Death ◽  
Caspase 8 ◽  
Multiple Cell

Matrix metalloproteinase 9 regulates cell death following pilocarpine-induced seizures in the developing brain

2012 ◽  
Vol 48 (3) ◽  
pp. 339-347 ◽  
Author(s):  
Yvonne Hoehna ◽  
Ortrud Uckermann ◽  
Hella Luksch ◽  
Vanya Stefovska ◽  
Jenny Marzahn ◽  
...  
Keyword(s):  
Cell Death ◽  
Matrix Metalloproteinase ◽  
Matrix Metalloproteinase 9 ◽  
Developing Brain ◽  
Metalloproteinase 9

Abstract 44: TAK1 Regulates Caspase 8 Activation and Necroptotic Signaling via Multiple Cell Death Checkpoints

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Xaioyun Guo ◽  
Haifeng Yin ◽  
Yi Chen ◽  
Lei Li ◽  
Jing Li ◽  
...  
Keyword(s):  
Cell Death ◽  
Adaptor Protein ◽  
Regulatory Mechanisms ◽  
Caspase 8 ◽  
Ubiquitin Proteasome Pathway ◽  
Pathological Conditions ◽  
Ubiquitin Proteasome ◽  
Multiple Cell ◽  
Proteasome Pathway

Necroptosis has emerged as a new form of programmed cell death implicated in a number of pathological conditions such as ischemic injury, neurodegenerative disease, and viral infection. Recent studies indicate that TGFβ-activated kinase 1 (TAK1) is nodal regulator of necroptotic cell death, but the underlying molecular regulatory mechanisms remain elusive. Here we reported that TAK1 regulates necroptotic signaling as well as caspase 8 activation through both NFκB-dependent and -independent mechanisms. Inhibition of TAK1 promoted TNFα-induced necroptosis through the induction of RIP1 phosphorylation/activation and necrosome formation, in the presence of ongoing caspase activation. Further, inhibition of TAK1 triggered two caspase 8 activation pathways through the induction of RIP1-FADD-caspase 8 complex as well as FLIP cleavage/degradation. Mechanistically, our data uncovered an essential role of the adaptor protein TRADD in caspase 8 activation and necrosome formation triggered by TAK1 inhibition. Moreover, ablation of the deubiqutinase CYLD prevented both apoptotic and necroptotic signaling induced by TAK1 inhibition, whereas deletion of the E3 ubiquitin ligase TRAF2 had the opposite effect. Finally, blocking the ubiquitin-proteasome pathway prevented the degradation of key necroptotic signaling proteins and necrosome formation. Thus we identified novel regulatory mechanisms underling the critical role of TAK1 in necroptotic signaling through regulation of multiple cell death checkpoints. Targeting key components of the necroptotic pathway (e.g., TRADD and CYLD) and the ubiquitin-proteasome pathway may represent novel therapeutic strategies for pathological conditions driven by necroptosis.

Genetic Regulation of RIPK1 and Necroptosis

2021 ◽  
Vol 55 (1) ◽  
pp. 235-263
Author(s):  
Daichao Xu ◽  
Chengyu Zou ◽  
Junying Yuan
Keyword(s):  
Cell Death ◽  
Protein Kinase ◽  
Genetic Regulation ◽  
Caspase 8 ◽  
Inflammatory Signaling ◽  
Interacting Protein ◽  
Multiple Factors ◽  
Cell Death Pathways ◽  
Upstream Regulator ◽  
Multiple Cell

The receptor-interacting protein kinase 1 (RIPK1) is recognized as a master upstream regulator that controls cell survival and inflammatory signaling as well as multiple cell death pathways, including apoptosis and necroptosis. The activation of RIPK1 kinase is extensively modulated by ubiquitination and phosphorylation, which are mediated by multiple factors that also control the activation of the NF-κB pathway. We discuss current findings regarding the genetic modulation of RIPK1 that controls its activation and interaction with downstream mediators, such as caspase-8 and RIPK3, to promote apoptosis and necroptosis. We also address genetic autoinflammatory human conditions that involve abnormal activation of RIPK1. Leveraging these new genetic and mechanistic insights, we postulate how an improved understanding of RIPK1 biology may support the development of therapeutics that target RIPK1 for the treatment of human inflammatory and neurodegenerative diseases.

scholarly journals Multiple cell death pathways as regulators of tumour initiation and progression

Oncogene ◽  
2004 ◽  
Vol 23 (16) ◽  
pp. 2746-2756 ◽  
Author(s):  
Marja Jäättelä
Keyword(s):  
Cell Death ◽  
Cell Death Pathways ◽  
Multiple Cell ◽  
Tumour Initiation

scholarly journals Protective effects of GPR37 via regulation of inflammation and multiple cell death pathways after ischemic stroke in mice

2019 ◽  
Vol 33 (10) ◽  
pp. 10680-10691 ◽  
Author(s):  
Myles R. McCrary ◽  
Michael Q. Jiang ◽  
Michelle M. Giddens ◽  
James Y. Zhang ◽  
Sharon Owino ◽  
...  
Keyword(s):  
Cell Death ◽  
Ischemic Stroke ◽  
Protective Effects ◽  
Cell Death Pathways ◽  
Multiple Cell
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