New Insights into the Cellular and Molecular Mechanisms of Cold Storage Injury

2004 ◽  
Vol 52 (5) ◽  
pp. 299-309 ◽  
Author(s):  
Ursula Rauen ◽  
Herbert de Groot
Keyword(s):  
Cold Storage ◽  
Molecular Mechanisms ◽  
Mitochondrial Permeability Transition ◽  
Ion Homeostasis ◽  
Permeability Transition ◽  
Solid Organ ◽  
Cellular Mechanisms ◽  
Hypothermic Injury ◽  
Preservation Solutions ◽  
Induced Apoptosis

Solid organ grafts, but also other biologic materials requiring storage for a few hours to a few days, are usually stored under hypothermic conditions. To decrease graft injury during cold storage, organ preservation solutions were developed many years ago. However, since then, modern biochemical and cell biologic methods have allowed further insights into the molecular and cellular mechanisms of cold storage injury, including further insights into alterations of the cellular ion homeostasis, the occurrence of a mitochondrial permeability transition, and the occurrence of free-radical-mediated hypothermic injury and cold-induced apoptosis. These new aspects of cold storage injury, which are not covered by preservation solutions in current clinical use and offer the potential for improvement of organ and tissue preservation, are presented here.

scholarly journals RIPK1 Coordinates Bone Marrow Mesenchymal Stem Cell Survival by Maintaining Mitochondrial Homeostasis via p53

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Qing Tian ◽  
Chen Cao ◽  
Weijian Qiu ◽  
Han Wu ◽  
Lijun Zhou ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Mitochondrial Dysfunction ◽  
Molecular Mechanisms ◽  
Mitochondrial Permeability Transition ◽  
Permeability Transition Pore ◽  
Permeability Transition ◽  
Bone Marrow Mscs ◽  
Induced Apoptosis

Survival of mesenchymal stem cells in the bone marrow is essential for bone marrow microenvironment homeostasis, but the molecular mechanisms remain poorly understood. RIPK1 has emerged as a critical molecule of programmed cell death in tissue homeostasis. However, little is known about the regulation of RIPK1 on bone marrow mesenchymal stem cells (MSCs). Here, we have investigated for the first time the role of RIPK1 in bone marrow MSCs. We have found that RIPK1 knockdown suppressed proliferation, differentiation, and migration in bone marrow MSCs. Furthermore, RIPK1 knockdown resulted in the opening of mitochondrial permeability transition pore (mPTP) and mtDNA damage, leading to mitochondrial dysfunction, and consequently induced apoptosis and necroptosis in bone marrow MSCs. Moreover, we identified that the p53-PUMA axis pathway was involved in mitochondrial dysfunction in RIPK1-deficient bone marrow MSCs. Together, our findings highlighted that RIPK1 was indispensable for bone marrow MSC survival.

scholarly journals Hepatitis B Virus Replication Is Associated with an HBx-Dependent Mitochondrion-Regulated Increase in Cytosolic Calcium Levels

2007 ◽  
Vol 81 (21) ◽  
pp. 12061-12065 ◽  
Author(s):  
Stephanie L. McClain ◽  
Amy J. Clippinger ◽  
Rebecca Lizzano ◽  
Michael J. Bouchard
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Molecular Mechanisms ◽  
Mitochondrial Permeability Transition Pore ◽  
Mitochondrial Permeability Transition ◽  
Permeability Transition Pore ◽  
Permeability Transition ◽  
Cytosolic Calcium ◽  
Hbv Replication ◽  
B Virus

ABSTRACT The nonstructural hepatitis B virus (HBV) protein HBx has an important role in HBV replication and in HBV-associated liver disease. Many activities have been linked to HBx expression; however, the molecular mechanisms underlying many of these activities are unknown. One proposed HBx function is the regulation of cytosolic calcium. We analyzed calcium levels in HepG2 cells that expressed HBx or replicating HBV, and we demonstrated that HBx, expressed in the absence of other HBV proteins or in the context of HBV replication, elevates cytosolic calcium. We linked this elevation of cytosolic calcium to the association of HBx with the mitochondrial permeability transition pore.

scholarly journals Preservation Solutions for Kidney Transplantation: History, Advances and Mechanisms

2019 ◽  
Vol 28 (12) ◽  
pp. 1472-1489 ◽  
Author(s):  
Yimeng Chen ◽  
Jian Shi ◽  
Terry C. Xia ◽  
Renfang Xu ◽  
Xiaozhou He ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Cold Storage ◽  
Solid Organ Transplantation ◽  
Atp Depletion ◽  
Solid Organ ◽  
Hypoxic Injury ◽  
The Past ◽  
Molecular Events ◽  
Preservation Solutions ◽  
Medical Advances

Solid organ transplantation was one of the greatest medical advances during the past few decades. Organ preservation solutions have been applied to diminish ischemic/hypoxic injury during cold storage and improve graft survival. In this article, we provide a general review of the history and advances of preservation solutions for kidney transplantation. Key components of commonly used solutions are listed, and effective supplementations for current available preservation solutions are discussed. At cellular and molecular levels, further insights were provided into the pathophysiological mechanisms of effective ingredients against ischemic/hypoxic renal injury during cold storage. We pay special attention to the cellular and molecular events during transplantation, including ATP depletion, acidosis, mitochondrial dysfunction, oxidative stress, inflammation, and other intracellular mechanisms.

scholarly journals The Mitochondrial Permeability Transition Is Required for Tumor Necrosis Factor Alpha-Mediated Apoptosis and Cytochrome c Release

1998 ◽  
Vol 18 (11) ◽  
pp. 6353-6364 ◽  
Author(s):  
Cynthia A. Bradham ◽  
Ting Qian ◽  
Konrad Streetz ◽  
Christian Trautwein ◽  
David A. Brenner ◽  
...  
Keyword(s):  
Cell Death ◽  
Tumor Necrosis ◽  
Caspase 3 ◽  
Mitochondrial Permeability Transition ◽  
Permeability Transition ◽  
Necrosis Factor Alpha ◽  
Mitochondrial Permeability ◽  
Factor Alpha ◽  
Induced Apoptosis ◽  
Necrosis Factor

ABSTRACT This study assesses the controversial role of the mitochondrial permeability transition (MPT) in apoptosis. In primary rat hepatocytes expressing an IκB superrepressor, tumor necrosis factor alpha (TNFα) induced apoptosis as shown by nuclear morphology, DNA ladder formation, and caspase 3 activation. Confocal microscopy showed that TNFα induced onset of the MPT and mitochondrial depolarization beginning 9 h after TNFα treatment. Initially, depolarization and the MPT occurred in only a subset of mitochondria; however, by 12 h after TNFα treatment, virtually all mitochondria were affected. Cyclosporin A (CsA), an inhibitor of the MPT, blocked TNFα-mediated apoptosis and cytochrome c release. Caspase 3 activation, cytochrome c release, and apoptotic nuclear morphological changes were induced after onset of the MPT and were prevented by CsA. Depolarization and onset of the MPT were blocked in hepatocytes expressing ΔFADD, a dominant negative mutant of Fas-associated protein with death domain (FADD), or crmA, a natural serpin inhibitor of caspases. In contrast, Asp-Glu-Val-Asp-cho, an inhibitor of caspase 3, did not block depolarization or onset of the MPT induced by TNFα, although it inhibited cell death completely. In conclusion, the MPT is an essential component in the signaling pathway for TNFα-induced apoptosis in hepatocytes which is required for both cytochrome c release and cell death and functions downstream of FADD and crmA but upstream of caspase 3.

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