scholarly journals Polyamines directly induce release of cytochrome c from heart mitochondria

2000 ◽  
Vol 347 (3) ◽  
pp. 875-880 ◽  
Author(s):  
Claudio STEFANELLI ◽  
Ivana STANIC' ◽  
Maddalena ZINI ◽  
Francesca BONAVITA ◽  
Flavio FLAMIGNI ◽  
...  
Keyword(s):  
Cytochrome C ◽  
Permeability Transition ◽  
Isolated Rat Heart ◽  
Heart Mitochondria ◽  
Cardiac Cell ◽  
Cytochrome C Release ◽  
Free Model ◽  
Discrete Amount ◽  
Rat Heart Mitochondria ◽  
Selective Process

Cytochrome c release from mitochondria to the cytosol represents a critical step in apoptosis, correlated to the activation of the caspase cascade. In this report, we show that addition of micromolar concentrations of polyamines to isolated rat heart mitochondria induces the release of cytochrome c. Spermine, which is effective at concentrations of 10-100 μM, is more potent than spermidine, whereas putrescine has no effect up to 1 mM. The release of cytochrome c caused by spermine is a rapid, saturable and selective process that is independent of mitochondria damage. Spermine, unlike polylysine, is able to release a discrete amount of cytochrome c from intact, functional mitochondria. The cytochrome c-releasing power of spermine is not affected by cyclosporin A, differently from the effect of permeability transition inducers. In a cardiac cell-free model of apoptosis, the latent caspase activity of cytosolic extracts from cardiomyocytes could be activated by cytochrome c released from spermine-treated heart mitochondria. These data indicate a novel mechanism of cytochrome c release from the mitochondrion, and suggest that prolonged and sustained elevation of polyamines, characteristic of some pathologies such as heart hypertrophy, could be involved in the development of apoptosis.

scholarly journals Mesalazine Induces Oxidative Stress and Cytochrome c Release in Isolated Rat Heart Mitochondria: An Analysis of Cardiotoxic Effects

2020 ◽  
Vol 39 (3) ◽  
pp. 241-247
Author(s):  
Ahmad Salimi ◽  
Farnaz Bahreini ◽  
Zhaleh Jamali ◽  
Jalal Pourahmad
Keyword(s):  
Cytochrome C ◽  
Rat Heart ◽  
Isolated Rat Heart ◽  
Mitochondrial Swelling ◽  
Heart Mitochondria ◽  
Cytochrome C Release ◽  
Mitochondrial Ros ◽  
Ros Formation ◽  
Rat Heart Mitochondria ◽  
Inflammatory Bowel

Mesalazine is widely used in the management of inflammatory bowel disease. Previous studies reported that mesalazine-induced cardiotoxicity is a rare, potentially fatal complication. Mitochondria play an important role in myocardial tissue homeostasis. Deterioration in mitochondrial function will eventually lead to cardiomyocyte death and consequently cardiovascular dysfunction. The aim of the current study was to investigate the effects of mesalazine on rat heart mitochondria. Rat heart mitochondria were isolated by mechanical lysis and differential centrifugation. Parameters of mitochondrial toxicity including succinate dehydrogenase (SDH) activity, reactive oxygen species (ROS) formation, mitochondrial membrane potential (MMP) collapse, mitochondrial swelling, and cytochrome c release were evaluated. Results revealed that mesalazine induced a concentration- and time-dependent rise in mitochondrial ROS formation, inhibition of SDH, MMP collapse, mitochondrial swelling, and cytochrome c release in rat heart mitochondria. These results indicate that the cardiotoxic effects of mesalazine are most likely associated with mitochondrial dysfunction and ROS formation, which finally ends in cytochrome c release signaling and induction of apoptosis.

Mitochondrial cytochrome c oxidase is inhibited by ATP only at very high ATP/ADP ratios

2017 ◽  
Vol 398 (7) ◽  
pp. 737-750 ◽  
Author(s):  
Rabia Ramzan ◽  
Andreas K. Schaper ◽  
Petra Weber ◽  
Annika Rhiel ◽  
Muhammad Saad Siddiq ◽  
...  
Keyword(s):  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Rat Heart ◽  
Isolated Rat Heart ◽  
Heart Mitochondria ◽  
Tween 20 ◽  
Activity Measurements ◽  
Atp Inhibition ◽  
Rat Heart Mitochondria ◽  
Very High

Abstract In the past, divergent results have been reported based on different methods and conditions used for enzymatic activity measurements of cytochrome c oxidase (CytOx). Here, we analyze in detail and show comparable and reproducible polarographic activity measurements of ATP-dependent inhibition of CytOx kinetics in intact and non-intact rat heart mitochondria and mitoplasts. We found that this mechanism is always present in isolated rat heart mitochondria and mitoplasts; however, it is measurable only at high ATP/ADP ratios using optimal protein concentrations. In the kinetics assay, measurement of this mechanism is independent of presence or absence of Tween-20 and the composition of measuring buffer. Furthermore, the effect of atractyloside on intact rat heart mitochondria confirms that (i) ATP inhibition occurs under uncoupled conditions [in the presence of carbonly cyanide m-chlorophenyl hydrazone (CCCP)] when the classical respiratory control is absent and (ii) high ATP/ADP ratios in the matrix as well as in the cytosolic space are required for full ATP inhibition of CytOx. Additionally, ATP inhibition measured in intact mitochondria extends in the presence of oligomycin, thus indicating further that the problem to measure the inhibitory effect of ATP on CytOx is apparently due to the lack of very high ATP/ADP ratios in isolated mitochondria.

Effect of chronic contractile activity on SS and IMF mitochondrial apoptotic susceptibility in skeletal muscle

2007 ◽  
Vol 292 (3) ◽  
pp. E748-E755 ◽  
Author(s):  
Peter J. Adhihetty ◽  
Vladimir Ljubicic ◽  
David A. Hood
Keyword(s):  
Skeletal Muscle ◽  
Cytochrome C ◽  
Manganese Superoxide Dismutase ◽  
Mitochondrial Permeability Transition ◽  
Contractile Activity ◽  
Permeability Transition Pore ◽  
Permeability Transition ◽  
Ros Production ◽  
Cytochrome C Release ◽  
Apoptosis Inducing Factor

Chronic contractile activity of skeletal muscle induces an increase in mitochondria located in proximity to the sarcolemma [subsarcolemmal (SS)] and in mitochondria interspersed between the myofibrils [intermyofibrillar (IMF)]. These are energetically favorable metabolic adaptations, but because mitochondria are also involved in apoptosis, we investigated the effect of chronic contractile activity on mitochondrially mediated apoptotic signaling in muscle. We hypothesized that chronic contractile activity would provide protection against mitochondrially mediated apoptosis despite an elevation in the expression of proapoptotic proteins. To induce mitochondrial biogenesis, we chronically stimulated (10 Hz; 3 h/day) rat muscle for 7 days. Chronic contractile activity did not alter the Bax/Bcl-2 ratio, an index of apoptotic susceptibility, and did not affect manganese superoxide dismutase levels. However, contractile activity increased antiapoptotic 70-kDa heat shock protein and apoptosis repressor with a caspase recruitment domain by 1.3- and 1.4-fold ( P < 0.05), respectively. Contractile activity elevated SS mitochondrial reactive oxygen species (ROS) production 1.4- and 1.9-fold ( P < 0.05) during states IV and III respiration, respectively, whereas IMF mitochondrial state IV ROS production was suppressed by 28% ( P < 0.05) and was unaffected during state III respiration. Following stimulation, exogenous ROS treatment produced less cytochrome c release (25–40%) from SS and IMF mitochondria, and also reduced apoptosis-inducing factor release (≈30%) from IMF mitochondria, despite higher inherent cytochrome c and apoptosis-inducing factor expression. Chronic contractile activity did not alter mitochondrial permeability transition pore (mtPTP) components in either subfraction. However, SS mitochondria exhibited a significant increase in the time to Vmax of mtPTP opening. Thus, chronic contractile activity induces predominantly antiapoptotic adaptations in both mitochondrial subfractions. Our data suggest the possibility that chronic contractile activity can exert a protective effect on mitochondrially mediated apoptosis in muscle.

scholarly journals Metformin inhibits mitochondrial permeability transition and cell death: a pharmacological in vitro study

2004 ◽  
Vol 382 (3) ◽  
pp. 877-884 ◽  
Author(s):  
Bruno GUIGAS ◽  
Dominique DETAILLE ◽  
Christiane CHAUVIN ◽  
Cécile BATANDIER ◽  
Frédéric De OLIVEIRA ◽  
...  
Keyword(s):  
Cell Death ◽  
Cytochrome C ◽  
Mitochondrial Permeability Transition ◽  
Permeability Transition ◽  
Cytochrome C Release ◽  
Intact Cells ◽  
Human Carcinoma ◽  
Butyl Hydroperoxide ◽  
Mitochondrial Permeability ◽  
New Findings

Metformin, a drug widely used in the treatment of Type II diabetes, has recently received attention owing to new findings regarding its mitochondrial and cellular effects. In the present study, the effects of metformin on respiration, complex 1 activity, mitochondrial permeability transition, cytochrome c release and cell death were investigated in cultured cells from a human carcinoma-derived cell line (KB cells). Metformin significantly decreased respiration both in intact cells and after permeabilization. This was due to a mild and specific inhibition of the respiratory chain complex 1. In addition, metformin prevented to a significant extent mitochondrial permeability transition both in permeabilized cells, as induced by calcium, and in intact cells, as induced by the glutathione-oxidizing agent t-butyl hydroperoxide. This effect was equivalent to that of cyclosporin A, the reference inhibitor. Finally, metformin impaired the t-butyl hydroperoxide-induced cell death, as judged by Trypan Blue exclusion, propidium iodide staining and cytochrome c release. We propose that metformin prevents the permeability transition-related commitment to cell death in relation to its mild inhibitory effect on complex 1, which is responsible for a decreased probability of mitochondrial permeability transition.

scholarly journals Bax-induced Cytochrome C Release from Mitochondria Is Independent of the Permeability Transition Pore but Highly Dependent on Mg2+ Ions

1998 ◽  
Vol 143 (1) ◽  
pp. 217-224 ◽  
Author(s):  
Robert Eskes ◽  
Bruno Antonsson ◽  
Astrid Osen-Sand ◽  
Sylvie Montessuit ◽  
Christoph Richter ◽  
...  
Keyword(s):  
Cytochrome C ◽  
Cyclosporin A ◽  
Mitochondrial Permeability Transition Pore ◽  
Mitochondrial Permeability Transition ◽  
Permeability Transition Pore ◽  
Permeability Transition ◽  
Cytochrome C Release ◽  
Mitochondrial Permeability ◽  
Isolated Mitochondria ◽  
Mammalian Homologue

Bcl-2 family members either promote or repress programmed cell death. Bax, a death-promoting member, is a pore-forming, mitochondria-associated protein whose mechanism of action is still unknown. During apoptosis, cytochrome C is released from the mitochondria into the cytosol where it binds to APAF-1, a mammalian homologue of Ced-4, and participates in the activation of caspases. The release of cytochrome C has been postulated to be a consequence of the opening of the mitochondrial permeability transition pore (PTP). We now report that Bax is sufficient to trigger the release of cytochrome C from isolated mitochondria. This pathway is distinct from the previously described calcium-inducible, cyclosporin A–sensitive PTP. Rather, the cytochrome C release induced by Bax is facilitated by Mg2+ and cannot be blocked by PTP inhibitors. These results strongly suggest the existence of two distinct mechanisms leading to cytochrome C release: one stimulated by calcium and inhibited by cyclosporin A, the other Bax dependent, Mg2+ sensitive but cyclosporin insensitive.

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