scholarly journals A digitized-fluorescence-imaging study of mitochondrial Ca2+ increase by doxorubicin in cardiac myocytes

1992 ◽  
Vol 281 (3) ◽  
pp. 871-878 ◽  
Author(s):  
E Chacon ◽  
R Ulrich ◽  
D Acosta
Keyword(s):  
Membrane Potential ◽  
Energy Conservation ◽  
Fluorescence Imaging ◽  
Cardiac Myocytes ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Cell Injury ◽  
Cultured Cells ◽  
Imaging Study

The objective of the present study was to investigate the role of mitochondrial Ca2+ in doxorubicin-induced cell injury. The effect of doxorubicin on cultured cells was investigated by digitized fluorescence imaging. The Ca2+ sensitive fluorescent dye fura-2 was used to estimate cytosolic, mitochondrial and total cellular Ca2+. Rhodamine 123 was used to estimate the mitochondrial membrane potential, and cellular ATP was determined by h.p.l.c. The data showed that doxorubicin induced greater-than-2-fold increases in mitochondrial Ca2+ before changes in cytosolic Ca2+ could be detected. An increase in mitochondrial Ca2+ paralleled the observed dissipation in mitochondrial membrane potential. Cellular ATP levels appeared to decrease as a result of mitochondrial dysfunction, which in turn produced greater-than-2-fold increases in cytosolic Ca2+. The data suggest that doxorubicin-induced alterations in mitochondrial Ca2+ homoeostasis are associated with a dissipation in energy conservation, which may result in cell injury.

Modulation of neuronal mitochondrial membrane potential by the NMDA receptor: role of arachidonic acid

1997 ◽  
Vol 777 (1-2) ◽  
pp. 69-74 ◽  
Author(s):  
Antonio Camins ◽  
Francesc X Sureda ◽  
Cecilia Gabriel ◽  
Mercè Pallàs ◽  
Elena Escubedo ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Membrane Potential ◽  
Nmda Receptor ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane

The role of mitochondrial membrane potential in ischemic heart failure

Mitochondrion ◽  
2011 ◽  
Vol 11 (5) ◽  
pp. 700-706 ◽  
Author(s):  
Bernhard Kadenbach ◽  
Rabia Ramzan ◽  
Rainer Moosdorf ◽  
Sebastian Vogt
Keyword(s):  
Heart Failure ◽  
Membrane Potential ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Ischemic Heart ◽  
Ischemic Heart Failure

scholarly journals NSAID-induced injury of gastric epithelial cells is reversible: roles of mitochondria, AMP kinase, NGF, and PGE2

2019 ◽  
Vol 317 (6) ◽  
pp. G862-G871
Author(s):  
Amrita Ahluwalia ◽  
Neil Hoa ◽  
Michael K. Jones ◽  
Andrzej S. Tarnawski
Keyword(s):  
Membrane Potential ◽  
Nerve Growth Factor ◽  
Epithelial Cells ◽  
Cell Viability ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Cell Injury ◽  
Prostaglandin E ◽  
Gastric Epithelial Cells ◽  
Amp Kinase

Nonsteroidal anti-inflammatory drugs (NSAIDs) such as diclofenac (DFN) and indomethacin (INDO) are extensively used worldwide. Their main side effects are injury of the gastrointestinal tract, including erosions, ulcers, and bleeding. Since gastric epithelial cells (GEPCs) are crucial for mucosal defense and are the major target of injury, we examined the extent to which DFN- and INDO-induced GEPC injury can be reversed by nerve growth factor (NGF), 16,16 dimethyl prostaglandin E2 (dmPGE2), and 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), the pharmacological activator of the metabolic sensor AMP kinase (AMPK). Cultured normal rat gastric mucosal epithelial (RGM1) cells were treated with PBS (control), NGF, dmPGE2, AICAR, and/or NSAID (DFN or INDO) for 1–4 h. We examined cell injury by confocal microscopy, cell death/survival using calcein AM, mitochondrial membrane potential using MitoTracker, and phosphorylation of AMPK by Western blotting. DFN and INDO treatment of RGM1 cells for 2 h decreased mitochondrial membrane potential and cell viability. NGF posttreatment (initiated 1 or 2 h after DFN or INDO) reversed the dissipation of mitochondrial membrane potential and cell injury caused by DFN and INDO and increased cell viability versus cells treated for 4 h with NSAID alone. Pretreatment with dmPGE2 and AICAR significantly protected these cells from DFN- and INDO-induced injury, whereas dmPGE2 and AICAR posttreatment (initiated 1 h after NSAID treatment) reversed cell injury and significantly increased cell viability and rescued the cells from NSAID-induced mitochondrial membrane potential reduction. DFN and INDO induce extensive mitochondrial injury and GEPC death, which can be significantly reversed by NGF, dmPGE2, and AICAR. NEW & NOTEWORTHY This study demonstrated that mitochondria are key targets of diclofenac- and indomethacin-induced injury of gastric epithelial cells and that diclofenac and indomethacin injury can be prevented and, importantly, also reversed by treatment with nerve growth factor, 16,16 dimethyl prostaglandin E2, and 5-aminoimidazole-4-carboxamide ribonucleotide.

scholarly journals 2P243 The role of cyclophilin D on persistence of mitochondrial membrane potential

2004 ◽  
Vol 44 (supplement) ◽  
pp. S170
Author(s):  
H. Suzuki ◽  
K. Machida ◽  
K. Higashino ◽  
C. Fujita ◽  
H. Osada ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Cyclophilin D

Mitochondrial KATP channel activation reduces anoxic injury by restoring mitochondrial membrane potential

2001 ◽  
Vol 281 (3) ◽  
pp. H1295-H1303 ◽  
Author(s):  
Meifeng Xu ◽  
Yigang Wang ◽  
Ahmar Ayub ◽  
Muhammad Ashraf
Keyword(s):  
Membrane Potential ◽  
Cytochrome C ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Cell Injury ◽  
Mitochondrial Permeability Transition ◽  
Ischemia Reperfusion ◽  
Selective Inhibitor ◽  
Atp Depletion ◽  
Channel Activation

Mitochondrial membrane potential (ΔΨm) is severely compromised in the myocardium after ischemia-reperfusion and triggers apoptotic events leading to cell demise. This study tests the hypothesis that mitochondrial ATP-sensitive K+ (mitoKATP) channel activation prevents the collapse of ΔΨm in myocytes during anoxia-reoxygenation (A-R) and is responsible for cell protection via inhibition of apoptosis. After 3-h anoxia and 2-h reoxygenation, the cultured myocytes underwent extensive damage, as evidenced by decreased cell viability, compromised membrane permeability, increased apoptosis, and decreased ATP concentration. Mitochondria in A-R myocytes were swollen and fuzzy as shown after staining with Mito Tracker Orange CMTMRos and in an electron microscope and exhibited a collapsed ΔΨm, as monitored by 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolcarbocyanine iodide (JC-1). Cytochrome c was released from mitochondria into the cytosol as demonstrated by cytochrome cimmunostaining. Activation of mitoKATP channel with diazoxide (100 μmol/l) resulted in a significant protection against mitochondrial damage, ATP depletion, cytochrome c loss, and stabilized ΔΨm. This protection was blocked by 5-hydroxydecanoate (500 μmol/l), a mitoKATPchannel-selective inhibitor, but not by HMR-1098 (30 μmol/l), a putative sarcolemmal KATP channel-selective inhibitor. Dissipation of ΔΨm also leads to opening of mitochondrial permeability transition pore, which was prevented by cyclosporin A. The data support the hypothesis that A-R disrupts ΔΨm and induces apoptosis, which are prevented by the activation of the mitoKATP channel. This further emphasizes the therapeutic significance of mitoKATP channel agonists in the prevention of ischemia-reperfusion cell injury.

scholarly journals The Interferon Stimulator Mitochondrial Antiviral Signaling Protein Facilitates Cell Death by Disrupting the Mitochondrial Membrane Potential and by Activating Caspases

2009 ◽  
Vol 84 (5) ◽  
pp. 2421-2431 ◽  
Author(s):  
Chia-Yi Yu ◽  
Ruei-Lin Chiang ◽  
Tsung-Hsien Chang ◽  
Ching-Len Liao ◽  
Yi-Ling Lin
Keyword(s):  
Cell Death ◽  
Membrane Potential ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Caspase Cleavage ◽  
Infected Cells ◽  
Mitochondrial Antiviral Signaling ◽  
Antiviral Innate Immunity ◽  
Viral Components

ABSTRACT Interferon (IFN) signaling is initiated by the recognition of viral components by host pattern recognition receptors. Dengue virus (DEN) triggers IFN-β induction through a molecular mechanism involving the cellular RIG-I/MAVS signaling pathway. Here we report that the MAVS protein level is reduced in DEN-infected cells and that caspase-1 and caspase-3 cleave MAVS at residue D429. In addition to its well-known function in IFN induction, MAVS is also a proapoptotic molecule that triggers disruption of the mitochondrial membrane potential and activation of caspases. Although different domains are required for the induction of cytotoxicity and IFN, caspase cleavage at residue 429 abolished both functions of MAVS. The apoptotic role of MAVS in viral infection and double-stranded RNA (dsRNA) stimulation was demonstrated in cells with reduced endogenous MAVS expression induced by RNA interference. Even though IFN-β promoter activation was largely suppressed, DEN production was not affected greatly in MAVS knockdown cells. Instead, DEN- and dsRNA-induced cell death and caspase activation were delayed and attenuated in the cells with reduced levels of MAVS. These results reveal a new role of MAVS in the regulation of cell death beyond its well-known function of IFN induction in antiviral innate immunity.

scholarly journals Rise in cytosolic Ca2+ and collapse of mitochondrial potential in anoxic, but not hypoxic, rat proximal tubules.

1996 ◽  
Vol 7 (11) ◽  
pp. 2348-2356
Author(s):  
S M Peters ◽  
M J Tijsen ◽  
R J Bindels ◽  
C H Van Os ◽  
J F Wetzels
Keyword(s):  
Membrane Potential ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Cell Injury ◽  
Cell Damage ◽  
Energy State ◽  
Oxygen Deprivation ◽  
Proximal Tubules ◽  
Rhodamine 123 ◽  
Anoxic Conditions

It has been suggested that ischemic renal proximal tubular cell injury is mediated by an increase in cytosolic calcium concentrations ((Ca2+)i). However, measurements of (Ca2+)i in rat or rabbit proximal tubules exposed to hypoxia or anoxia have yielded ambiguous results. This study explored the possibility that the severity of oxygen deprivation and the energy state of the mitochondria are important determinants of (Ca2+)i. To this end, (Ca2+)i (measured with fura-2) and the mitochondrial membrane potential (measured with rhodamine 123) were studied simultaneously in individual rat proximal tubules in hypoxic and anoxic conditions. (Ca2+)i did not change during hypoxia, but increased rapidly during anoxia. Increases in (Ca2+)i were only observed in parallel with a decrease of rhodamine 123 fluorescence, which indicates a collapse of the mitochondrial membrane potential. The increase in (Ca2+)i during anoxia was prevented by incubating the tubules in a low Ca2+ medium, which did not interfere with the collapse of the mitochondrial membrane potential. Both hypoxic and anoxic incubation led to cell death, as assessed by the fluorescent dye propidium iodide. These results clearly demonstrate that the level of oxygen deprivation is critical in determining changes in (Ca2+)i. Because cell damage occurred in both hypoxic and anoxic conditions. It was concluded that an increase in (Ca2+)i is not a necessary prerequisite for the development of ischemic cell injury.

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