scholarly journals Regulated Cell Death Seen through the Lens of Islet Transplantation

2018 ◽  
Vol 27 (6) ◽  
pp. 890-901 ◽  
Author(s):  
Antonio Bruni ◽  
Stefan Bornstein ◽  
Andreas Linkermann ◽  
A. M. James Shapiro
Keyword(s):  
Cell Death ◽  
Islet Transplantation ◽  
Apoptotic Cell ◽  
Glycosylated Hemoglobin ◽  
Solid Organ Transplantation ◽  
Apoptotic Cell Death ◽  
Solid Organ ◽  
Cell Death Pathways ◽  
Regulated Cell Death ◽  
Clinical Islet Transplantation

Clinical islet transplantation effectively restores euglycemia and corrects glycosylated hemoglobin in labile type 1 diabetes mellitus (T1DM). Despite marked improvements in islet transplantation outcomes, acute islet cell death remains a substantial obstacle that compromises long-term engraftment outcomes. Multiple organ donors are routinely required to achieve insulin independence. Therapeutic agents that ameliorate cell death and/or control injury-related inflammatory cascades offer potential to improve islet transplant success. Apoptotic cell death has been identified as a major contributor to cellular demise and therapeutic strategies that subvert initiation and consequences of apoptotic cell death have shown promise in pre-clinical models. Indeed, in numerous pathologies and diseases apoptosis has been the most extensively described form of regulated cell death. However, recent identification of novel, alternative regulated cell death pathways in other disease states and solid organ transplantation suggest that these additional pathways may also have substantial relevance in islet transplantation. These regulated, non-apoptotic cell death pathways exhibit distinct biochemical characteristics but have yet to be fully characterized within islet transplantation. We review herein the various regulated cell death pathways and highlight their relative potential contributions to islet viability, engraftment failure and islet dysfunction.

scholarly journals IGF2: an endocrine hormone to improve islet transplant survival

2014 ◽  
Vol 221 (2) ◽  
pp. R41-R48 ◽  
Author(s):  
Amy Hughes ◽  
Darling Rojas-Canales ◽  
Chris Drogemuller ◽  
Nicolas H Voelcker ◽  
Shane T Grey ◽  
...  
Keyword(s):  
Cell Death ◽  
Islet Transplantation ◽  
Inflammatory Cytokine ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Pancreatic Islet Transplantation ◽  
Post Transplant ◽  
Islet Transplant ◽  
Clinical Islet Transplantation ◽  
Islet Survival

In the week following pancreatic islet transplantation, up to 50% of transplanted islets are lost due to apoptotic cell death triggered by hypoxic and pro-inflammatory cytokine-mediated cell stress. Thus, therapeutic approaches designed to protect islet cells from apoptosis could significantly improve islet transplant success. IGF2 is an anti-apoptotic endocrine protein that inhibits apoptotic cell death through the mitochondrial (intrinsic pathway) or via antagonising activation of pro-inflammatory cytokine signalling (extrinsic pathway), in doing so IGF2 has emerged as a promising therapeutic molecule to improve islet survival in the immediate post-transplant period. The development of novel biomaterials coated with IGF2 is a promising strategy to achieve this. This review examines the mechanisms mediating islet cell apoptosis in the peri- and post-transplant period and aims to identify the utility of IGF2 to promote islet survival and enhance long-term insulin independence rates within the setting of clinical islet transplantation.

Regulated necrosis: the expanding network of non-apoptotic cell death pathways

2014 ◽  
Vol 15 (2) ◽  
pp. 135-147 ◽  
Author(s):  
Tom Vanden Berghe ◽  
Andreas Linkermann ◽  
Sandrine Jouan-Lanhouet ◽  
Henning Walczak ◽  
Peter Vandenabeele
Keyword(s):  
Cell Death ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Cell Death Pathways ◽  
Regulated Necrosis

Multiple alphaII-spectrin breakdown products distinguish calpain and caspase dominated necrotic and apoptotic cell death pathways

APOPTOSIS ◽  
2009 ◽  
Vol 14 (11) ◽  
pp. 1289-1298 ◽  
Author(s):  
Zhiqun Zhang ◽  
Stephen F. Larner ◽  
Ming Cheng Liu ◽  
Wenrong Zheng ◽  
Ronald L. Hayes ◽  
...  
Keyword(s):  
Cell Death ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Cell Death Pathways

Abstract 5104: Identification of cancer-specific COPI inhibitors and their associated apoptotic cell death pathways

2014 ◽  
Author(s):  
David J. Oliver ◽  
Anusha Chaparala ◽  
Emeka Okafor ◽  
Carlos J. Camacho ◽  
Alexander S. Doemling ◽  
...  
Keyword(s):  
Cell Death ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Cell Death Pathways

scholarly journals Flipping the dogma – phosphatidylserine in non-apoptotic cell death

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Inbar Shlomovitz ◽  
Mary Speir ◽  
Motti Gerlic
Keyword(s):  
Cell Death ◽  
Inflammatory Cell ◽  
Unique Feature ◽  
Apoptotic Cell ◽  
Apoptotic Cells ◽  
Complete Understanding ◽  
Cell Death Pathways ◽  
Regulated Cell Death ◽  
Dying Cells ◽  
Outer Plasma Membrane

Abstract The exposure of phosphatidylserine (PS) on the outer plasma membrane has long been considered a unique feature of apoptotic cells. Together with other “eat me” signals, it enables the recognition and phagocytosis of dying cells (efferocytosis), helping to explain the immunologically-silent nature of apoptosis. Recently, however, PS exposure has also been reported in non-apoptotic forms of regulated inflammatory cell death, such as necroptosis, challenging previous dogma. In this review, we outline the evidence for PS exposure in non-apoptotic cells and extracellular vesicles (EVs), and discuss possible mechanisms based on our knowledge of apoptotic-PS exposure. In addition, we examine the outcomes of non-apoptotic PS exposure, including the reversibility of cell death, efferocytosis, and consequent inflammation. By examining PS biology, we challenge the established approach of distinguishing apoptosis from other cell death pathways by AnnexinV staining of PS externalization. Finally, we re-evaluate how PS exposure is thought to define apoptosis as an immunologically silent process distinct from other non-apoptotic and inflammatory cell death pathways. Ultimately, we suggest that a complete understanding of how regulated cell death processes affect the immune system is far from being fully elucidated. Graphical abstract

scholarly journals Zinc deficiency mediates alcohol-induced apoptotic cell death in the liver of rats through activating ER and mitochondrial cell death pathways

2015 ◽  
Vol 308 (9) ◽  
pp. G757-G766 ◽  
Author(s):  
Qian Sun ◽  
Wei Zhong ◽  
Wenliang Zhang ◽  
Qiong Li ◽  
Xiuhua Sun ◽  
...  
Keyword(s):  
Cell Death ◽  
Zinc Deficiency ◽  
Caspase 3 ◽  
Apoptotic Cell ◽  
Alcohol Exposure ◽  
Ethanol Exposure ◽  
Apoptotic Cell Death ◽  
Zinc Homeostasis ◽  
Initiation Factor ◽  
Cell Death Pathways

Hepatic zinc deficiency has been well documented in alcoholic patients, but the mechanisms by which zinc deficiency mediates cell death have not been well defined. The objectives of this study were to determine whether alcohol perturbs subcellular zinc homeostasis and how organelle zinc depletion may link with cell death pathways. Wistar rats were pair-fed with the Lieber-DeCarli control or ethanol diet for 5 mo. Chronic alcohol exposure significantly reduced zinc level in isolated hepatic endoplasmic reticulum (ER) and mitochondria. Among the detected zinc transporters, ER Zrt/Irt-like protein (ZIP)13 and mitochondrial ZIP8, which transport zinc from ER and mitochondria to cytosol, were significantly increased. Mitochondrial zinc transporter (ZnT) 4, which transports zinc from cytosol to mitochondria, was also increased. ER phosphorylated eukaryotic initiation factor 2α, activating transcription factor 4, and C/EBP homologous protein were significantly upregulated, and mitochondrial cytochrome c release and Bax insertion were detected in association with caspase-3 activation and apoptotic cell death. To define the role of zinc deficiency in ER and mitochondrial stress, H4IIEC3 cells were treated with 3 μM N,N,N′,N′-tetrakis (2-pyridylmethyl) ethylenediamine for 6 h with or without supplementation with zinc or N-acetylcysteine (NAC). The results demonstrated that zinc deprivation induced caspase-3 activation and apoptosis in association with ER and mitochondria dysfunction, which were inhibited by zinc as low as 10 μM but not by 2 mM NAC. These results suggest that chronic ethanol exposure induced in ER and mitochondrial zinc deficiency might activate intrinsic cell death signaling pathway, which could not be effectively rescued by antioxidant treatment.

scholarly journals Chk2-p53 and JNK in irradiation-induced cell death of hematopoietic progenitors and differentiated cells in Drosophila larval lymph gland

Biology Open ◽  
2021 ◽  
Author(s):  
Tram Thi Ngoc Nguyen ◽  
Jiwon Shim ◽  
Young-Han Song
Keyword(s):  
Dna Damage ◽  
Cell Death ◽  
Environmental Changes ◽  
Apoptotic Cell ◽  
Lymph Gland ◽  
Apoptotic Cell Death ◽  
Dna Double Strand Breaks ◽  
Hematopoietic Organ ◽  
Cell Death Pathways ◽  
Differentiated Cells

Ionizing radiation (IR) induces DNA double-strand breaks that activate the DNA damage response (DDR), which leads to cell cycle arrest, senescence, or apoptotic cell death. Understanding the DDR of stem cells is critical to tissue homeostasis and the survival of the organism. Drosophila hematopoiesis serves as a model system for sensing stress and environmental changes; however, their response to DNA damage remains largely unexplored. The Drosophila lymph gland is the larval hematopoietic organ, where stem-like progenitors proliferate and differentiate into mature blood cells called hemocytes. We found that apoptotic cell death was induced in progenitors and hemocytes after 40 Gy irradiation, with progenitors showing more resistance to IR-induced cell death compared to hemocytes at a lower dose. Furthermore, we found that Drosophila ATM (tefu), Chk2 (lok), p53, and reaper were necessary for IR-induced cell death in the progenitors. Notably, IR-induced cell death in mature hemocytes required tefu, Drosophila JNK (bsk), and reaper, but not lok or p53. In summary, we found that DNA damage induces apoptotic cell death in the late third instar larval lymph gland and identified lok/p53-dependent and -independent cell death pathways in progenitors and mature hemocytes, respectively.

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