Paradox of Oxygen-Radical-Dependent Cell Injury in the Hypoxic Liver Microcirculation

2015 ◽  
pp. 127-138 ◽  
Author(s):  
M. Suematsu ◽  
H. Suzuki ◽  
H. Ishii ◽  
M. Tsuchiya
Keyword(s):  
Cell Injury ◽  
Oxygen Radical ◽  
Liver Microcirculation ◽  
Dependent Cell

ATP depletion rather than mitochondrial depolarization mediates hepatocyte killing after metabolic inhibition

1994 ◽  
Vol 267 (1) ◽  
pp. C67-C74 ◽  
Author(s):  
A. L. Nieminen ◽  
A. K. Saylor ◽  
B. Herman ◽  
J. J. Lemasters
Keyword(s):  
Cell Death ◽  
Cell Injury ◽  
Rat Hepatocytes ◽  
Cell Killing ◽  
Atp Depletion ◽  
Mitochondrial Depolarization ◽  
Minimum Concentration ◽  
Atp Formation ◽  
Mitochondrial Atp Synthase ◽  
Dependent Cell

The importance of ATP depletion and mitochondrial depolarization in the toxicity of cyanide, oligomycin, and carbonyl cyanide m-cholorophenylhydrazone (CCCP), an uncoupler, was evaluated in rat hepatocytes. Oligomycin, an inhibitor of the reversible mitochondrial ATP synthase (F1F0-adenosinetriphosphatase), caused dose-dependent cell killing with 0.1 microgram/ml being the minimum concentration causing the maximum cell killing. Oligomycin also caused rapid ATP depletion without causing mitochondrial depolarization. Fructose (20 mM), a potent glycolytic substrate in liver, protected completely against oligomycin toxicity. CCCP (5 microM) also caused rapid killing of hepatocytes. Fructose retarded cell death caused by CCCP but failed to prevent lethal cell injury. Although oligomycin (1.0 microgram/ml) was lethally toxic by itself, in the presence of fructose it protected completely against CCCP-induced cell killing. Cyanide (2.5 mM), an inhibitor of mitochondrial respiration, caused rapid cell killing that was reversed by fructose. CCCP completely blocked fructose protection against cyanide, causing mitochondrial depolarization and rapid ATP depletion. In the presence of fructose and cyanide, oligomycin protected cells against CCCP-induced ATP depletion and cell death but did not prevent mitochondrial depolarization. In every instance, cell killing was associated with ATP depletion, whereas protection against lethal cell injury was associated with preservation of ATP. In conclusion, protection by fructose against toxicity of cyanide, oligomycin, and CCCP was mediated by glycolytic ATP formation rather than by preservation of the mitochondrial membrane potential. These findings support the hypothesis that inhibition of cellular ATP formation is a crucial event in the progression of irreversible cell injury.

scholarly journals Increased Uptake of Zinc in Malignant Cells is Associated with Enhanced Activation of MAPK Signalling and P53-Dependent Cell Injury

2008 ◽  
Vol 51 (1) ◽  
pp. 43-49 ◽  
Author(s):  
Emil Rudolf
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Cell Injury ◽  
Cell Damage ◽  
Zinc Homeostasis ◽  
Malignant Cells ◽  
Intracellular Zinc ◽  
Free Zinc ◽  
Dependent Cell ◽  
Zinc Levels

Excess intracellular zinc has been demonstrated to be responsible for cell injury and cell death in various experimental as well as clinical models. While the cells possess a system of mechanisms regulating intracellular zinc homeostasis, their saturation by acutely increased zinc levels or by a sustained exposure to elevated zinc levels results in liberation of free zinc stores within the cells and ultimate cell damage and cell death. Here we report that in Hep-2 malignant cells enhanced uptake of zinc causes activation of mitogen-activated protein kinase (MAPK) signaling with resulting p53-dependent cell injury which can be significantly prevented by specific p53 inhibition and by prevention of oxidative stress. Our observations are consistent with the view that subacutely increased intracellular free zinc levels stimulate via oxidative stress p53-dependent pathways which are responsible for the final cell damage in tumor cells.

scholarly journals Exosomes From miR-19b-3p-Modified ADSCs Inhibit Ferroptosis in Intracerebral Hemorrhage Mice

2021 ◽  
Vol 9 ◽  
Author(s):  
Xia Yi ◽  
Xiangqi Tang
Keyword(s):  
Intracerebral Hemorrhage ◽  
Cell Injury ◽  
Regulatory Protein ◽  
Luciferase Reporter ◽  
Cultured Neurons ◽  
Adipose Derived Stem Cells ◽  
Dependent Cell ◽  
Neurologic Function ◽  
Direct Target ◽  
The Impact

Objectives: Effective treatments for intracerebral hemorrhage (ICH) are limited until now. Ferroptosis, a novel form of iron-dependent cell death, is implicated in neurodegeneration diseases. Here, we attempted to investigate the impact of exosomes from miR-19b-3p-modified adipose-derived stem cells (ADSCs) on ferroptosis in ICH.Methods: Collagenase was used to induce a mouse model of ICH and hemin was used to induce ferroptosis in cultured neurons. Exosomes were isolated from mimic NC- or miR-19b-3p mimic-transfected ADSCs (ADSCs-MNC-Exos or ADSCs-19bM-Exos, respectively) and then administered to ICH mice or hemin-treated neurons. ICH damage was evaluated by assessing the neurological function of ICH mice and cell viability of neurons. Ferroptosis was evaluated in mouse brains or cultured neurons. The interaction between miR-19b-3p and iron regulatory protein 2 (IRP2) 3′-UTR was analyzed by performing luciferase reporter assay.Results: Ferroptosis occurred in ICH mice, which also exhibited decreased miR-19b-3p and increased IRP2 expression. IRP2 was a direct target of miR-19b-3p, and IRP2 expression was repressed by ADSCs-19bM-Exos. Importantly, ADSCs-19bM-Exos effectively attenuated hemin-induced cell injury and ferroptosis. Moreover, ADSCs-19bM-Exos administration significantly improved neurologic function and inhibited ferroptosis in ICH mice.Conclusion: Exosomes from miR-19b-3p-modified ADSCs inhibit ferroptosis in ICH mice.

scholarly journals Paradoxical enhancement of oxidative cell injury by overexpression of heme oxygenase-1 in an anchorage-dependent cell ECV304

2004 ◽  
Vol 93 (3) ◽  
pp. 552-562 ◽  
Author(s):  
Keiko Maruhashi ◽  
Yoshihito Kasahara ◽  
Kunio Ohta ◽  
Taizo Wada ◽  
Kazuhide Ohta ◽  
...  
Keyword(s):  
Heme Oxygenase ◽  
Cell Injury ◽  
Heme Oxygenase 1 ◽  
Dependent Cell

scholarly journals Transport–dependent cell injury in the S3 segment of the proximal tubule

1986 ◽  
Vol 29 (5) ◽  
pp. 1033-1037 ◽  
Author(s):  
Paul F. Shanley ◽  
Mayer Brezis ◽  
Katherine Spokes ◽  
Patricio Silva ◽  
Franklin H. Epstein ◽  
...  
Keyword(s):  
Proximal Tubule ◽  
Cell Injury ◽  
Dependent Cell ◽  
S3 Segment

scholarly journals Increased oxygen radical and eicosanoid formation in immune-mediated mesangial cell injury

1992 ◽  
Vol 42 (1) ◽  
pp. 69-74 ◽  
Author(s):  
Gerhard P. Oberle ◽  
Jan. Niemeyer ◽  
Friedrich Thaiss ◽  
Wilhelm Schoeppe ◽  
Rolf A.K. Stahl
Keyword(s):  
Cell Injury ◽  
Mesangial Cell ◽  
Oxygen Radical ◽  
Immune Mediated ◽  
Eicosanoid Formation

Methylglyoxal induces oxidative stress-dependent cell injury and up-regulation of interleukin-1β and nerve growth factor in cultured hippocampal neuronal cells

2004 ◽  
Vol 1006 (2) ◽  
pp. 157-167 ◽  
Author(s):  
Silvia Di Loreto ◽  
Valentina Caracciolo ◽  
Sabrina Colafarina ◽  
Pierluigi Sebastiani ◽  
Antonella Gasbarri ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nerve Growth Factor ◽  
Growth Factor ◽  
Cell Injury ◽  
Neuronal Cells ◽  
Interleukin 1Β ◽  
Nerve Growth ◽  
Dependent Cell ◽  
Stress Dependent
Sign in / Sign up

Export Citation Format

Share Document