scholarly journals Cd2+ -promoted mitochondrial permeability transition: a comparison with other heavy metals.

2004 ◽  
Vol 51 (2) ◽  
pp. 545-551 ◽  
Author(s):  
Elena A Belyaeva ◽  
Vadim V Glazunov ◽  
Sergey M Korotkov
Keyword(s):  
Heavy Metal Ions ◽  
Inhibitory Action ◽  
Mitochondrial Permeability Transition ◽  
Permeability Transition ◽  
Liver Mitochondria ◽  
Basal Respiration ◽  
Rat Liver Mitochondria ◽  
Isolated Rat Liver ◽  
Mitochondrial Permeability ◽  
Isolated Rat

We compared action of Cd(2+), Hg(2+), and Cu(2+) on isolated rat liver mitochondria in the absence of added Ca(2+) and P(i). The heavy-metal ions produced dose-dependently: (1) enhanced membrane permeabilization manifested in mitochondrial swelling and activation of basal respiration, (2) inhibition of uncoupler-stimulated respiration, and (3) membrane potential dissipation. Among the metals, Cu(2+) exhibited maximal stimulatory effect on basal respiration and minimal inhibitory action on DNP-uncoupled respiration whilst Cd(2+) promoted the strongest depression of uncoupled respiration and the largest swelling in NH(4)NO(3) medium. Dithiothreitol induced a basal respiration release if added after high [Cd(2+)] and [Hg(2+)], and the stimulation was CsA-insensitive.

scholarly journals Toxicity of Pb2+ on rat liver mitochondria induced by oxidative stress and mitochondrial permeability transition

2017 ◽  
Vol 6 (6) ◽  
pp. 822-830 ◽  
Author(s):  
Long Ma ◽  
Jun-Yi Liu ◽  
Jia-Xin Dong ◽  
Qi Xiao ◽  
Jie Zhao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Rat Liver ◽  
Mitochondrial Permeability Transition ◽  
Permeability Transition ◽  
Liver Mitochondria ◽  
Rat Liver Mitochondria ◽  
Isolated Rat Liver ◽  
Mitochondrial Permeability ◽  
Isolated Rat

Toxicities and mechanisms of Pb2+ on isolated rat liver mitochondria.

scholarly journals Fluorocitrate inhibition of aconitate hydratase and the tricarboxylate carrier of rat liver mitochondria

1973 ◽  
Vol 134 (1) ◽  
pp. 217-224 ◽  
Author(s):  
M. D. Brand ◽  
Susan M. Evans ◽  
J. Mendes-Mourão ◽  
J. B. Chappell
Keyword(s):  
Rat Liver ◽  
Inhibitory Action ◽  
Liver Mitochondria ◽  
Rat Liver Mitochondria ◽  
Exchange Reactions ◽  
Aconitate Hydratase ◽  
Isolated Rat Liver ◽  
Tricarboxylate Carrier ◽  
Hydratase Activity ◽  
Isolated Rat

1. The effect of biologically synthesized and purified fluorocitrate on the metabolism of tricarboxylate anions by isolated rat liver mitochondria was investigated, in relation to the claim by Eanes et al. (1972) that this fluoro compound inhibits the tricarboxylate carrier at concentrations at which it has little effect on the aconitate hydratase activity. 2. That the inhibitory action of fluorocitrate is at the level of the aconitate hydratase and not at the level of the tricarboxylate carrier is indicated by the following findings. Although the oxidation of citrate and cis-aconitate, but not that of isocitrate, was inhibited by fluorocitrate, the exchange of internal citrate for external citrate or l-malate was not. Had the tricarboxylate carrier been affected, these latter exchange reactions would have been inhibited. 3. By using aconitate hydratase solubilized from mitochondria it was found that with citrate as substrate the inhibition by fluorocitrate was partially competitive (Ki=3.4×10−8m), whereas with cis-aconitate as substrate the inhibition was partially non-competitive (Ki=3.0×10−8m).

scholarly journals Bisindolylpyrrole triggers transient mitochondrial permeability transitions to cause apoptosis in a VDAC1/2 and cyclophilin D-dependent manner via the ANT-associated pore

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Masami Koushi ◽  
Yasunori Aoyama ◽  
Yoshiko Kamei ◽  
Rei Asakai
Keyword(s):  
Mitochondrial Permeability Transition ◽  
Permeability Transition ◽  
Liver Mitochondria ◽  
Rat Liver Mitochondria ◽  
Dependent Manner ◽  
Cyclophilin D ◽  
Cytoprotective Effect ◽  
Mitochondrial Permeability ◽  
Sirna Knockdown ◽  
Pkc Activation

Abstract Bisindolylpyrrole at 0.1 μM is cytoprotective in 2% FBS that is counteracted by cyclosporin-A (CsA), an inhibitor of cyclophilin-D (CypD). We hypothesized that the cytoprotective effect might be due to transient mitochondrial permeability transition (tPT). This study tested the hypothesis that bisindolylpyrrole can trigger tPT extensively, thereby leading to cell death under certain conditions. Indeed, CsA-sensitive tPT-mediated apoptosis could be induced by bisindolylpyrrole at > 5 μM in HeLa cells cultured in 0.1% FBS, depending on CypD and VDAC1/2, as shown by siRNA knockdown experiments. Rat liver mitochondria also underwent swelling in response to bisindolylpyrrole, which proceeded at a slower rate than Ca2+-induced swelling, and which was blocked by the VDAC inhibitor tubulin and the ANT inhibitor bongkrekate, indicating the involvement of the ANT-associated, smaller pore. We examined why 0.1% FBS is a prerequisite for apoptosis and found that apoptosis is blocked by PKC activation, which is counteracted by the overexpressed defective PKCε. In mitochondrial suspensions, bisindolylpyrrole triggered CsA-sensitive swelling, which was suppressed selectively by pretreatment with PKCε, but not in the co-presence of tubulin. These data suggest that upon PKC inactivation the cytoprotective compound bisindolylpyrrole can induce prolonged tPT causing apoptosis in a CypD-dependent manner through the VDAC1/2-regulated ANT-associated pore.

Role of calcium and superoxide dismutase in sensitizing mitochondria to peroxynitrite-induced permeability transition

2004 ◽  
Vol 286 (1) ◽  
pp. H39-H46 ◽  
Author(s):  
Paul S. Brookes ◽  
Victor M. Darley-Usmar
Keyword(s):  
Superoxide Dismutase ◽  
Cytochrome C ◽  
Rat Liver ◽  
Permeability Transition ◽  
Liver Mitochondria ◽  
Rat Liver Mitochondria ◽  
Isolated Rat Liver ◽  
Ptp Opening ◽  
Isolated Rat

The mitochondrial permeability transition pore (PTP) is a membrane protein complex assembled and opened in response to Ca2+ and oxidants such as peroxynitrite (ONOO–). Opening the PTP is mechanistically linked to the release of cytochrome c, which participates in downstream apoptotic signaling. However, the molecular basis of the synergistic interactions between oxidants and Ca2+ in promoting the PTP are poorly understood and are addressed in the present study. In isolated rat liver mitochondria, it was found that the timing of the exposure of the isolated rat liver mitochondria to Ca2+ was a critical factor in determining the impact of ONOO– on PTP. Specifically, addition of Ca2+ alone, or ONOO– and then Ca2+, elicited similar low levels of PTP opening, whereas ONOO– alone was ineffective. In contrast, addition of Ca2+ and then ONOO– induced extensive PTP opening and cytochrome c release. Interestingly, Cu/Zn-superoxide dismutase enhanced pore opening through a mechanism independent of its catalytic activity. These data are consistent with a model in which Ca2+ reveals a molecular target that is now reactive with ONOO–. As a test of this hypothesis, tyrosine nitration was determined in mitochondria exposed to ONOO– alone or to Ca2+ and then ONOO–, and mitochondrial membrane proteins were analyzed using proteomics. These studies suggest protein targets revealed by Ca2+ include dehydrogenases and CoA-containing enzymes. These data are discussed in the context of the role of mitochondria, Ca2+, and ONOO– in apoptotic signaling.

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