Carboxyatractyloside increases the effect of oleate on mitochondrial permeability transition

Chávez, Edmundo; Zazueta, Cecilia; Garcı́a, Noemı́

doi:10.1016/s0014-5793(99)00128-3

Cited by 19 publications

(15 citation statements)

References 28 publications

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“…It is important to note that the effects obtained with NEM on the action of these inducers on pore opening present new information: (i) the NEM-induced inhibition of pore opening as induced by CAT and agaric acid, (ii) the fact that ANT's function is inhibited by CAT and agaric acid without opening of the non-specific pore, (iii) the stimulating effect by NEM on oleate-induced permeability transition, and (iv) the increased binding of EMA to the ADP/ATP carrier after the addition of oleate. The fact that NEM inhibited the effect of CAT on Ca 2+ efflux and mitochondrial swelling cannot be explained considering the argument that NEM inhibits the binding of CAT, as has been proposed [7,18]. This assumption emerges from the finding that carboxyatractyloside still inhibits ADP Fig.…”

Section: Discussionmentioning

confidence: 97%

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The Effect of N-Ethylmaleimide on Permeability Transition as Induced by Carboxyatractyloside, Agaric Acid, and Oleate

Garcı́a

Pavón

Chávez

2008

Cell Biochem Biophys

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In this work, we studied the effect of N-ethylmaleimide on permeability transition. The findings indicate that the amine inhibited the effects of carboxyatractyloside and agaric acid. It is known that these reagents interact with the adenine nucleotide carrier through the cytosolic side. When oleate, which interacts through the matrix side, was used it was found that the amine amplified the effects of oleate on permeability transition. The results also show that N-ethylmaleimide strengthened the inhibition induced by carboxyatractyloside, agaric acid, and oleate on ADP exchange. Furthermore, it was also found that oleate improved the binding of eosin-5-maleimide on the adenine nucleotide translocase.

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Section: Discussionmentioning

confidence: 97%

“…In turn, Mironova et al [17] showed that palmitic and steraric acids induce non-specific ion channels in black-lipid membranes. It has also been reported that oleate induces permeability transition, through a mechanism that is inhibited by cyclosporin A [18].…”

Section: Introductionmentioning

confidence: 95%

The Effect of N-Ethylmaleimide on Permeability Transition as Induced by Carboxyatractyloside, Agaric Acid, and Oleate

Garcı́a

Pavón

Chávez

2008

Cell Biochem Biophys

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“…ANT forms the PT pore when associated with cyclophilin-D in the mitochondrial matrix and the nonselective voltage-dependent anion channel in the mitochondrial outer membrane (voltage-dependent anion channel is located at the contact points between the inner membrane cristae and the outer membrane). Cyclosporin-A (a ligand of with cyclophilin-D) and some inhibitors of the ANT inhibit PT pore formation, whereas other ANT inhibitors increase the probability of pore opening (Zamzami et al, 1996;Chavez et al, 1999).…”

Section: Mechanism Of Action Of Clodronate 1259mentioning

confidence: 99%

“…The effect of ANT inhibition on PT pore formation depends on whether the ligands bind to the m-state or c-state. Ligands binding to the m-state inhibit the formation of the PT pore and ligands binding to the c-state induce the formation of the PT pore (Zamzami et al, 1996;Chavez et al, 1999). If AppCCl 2 p acts as an enhancer of PT pore formation, it would be expected to do this by acting as a ligand binding to the c-state of the ANT (i.e., acting on the cytosolic side of the mitochondrial membrane).…”

Section: Mechanism Of Action Of Clodronate 1259mentioning

confidence: 99%

Further Insight into Mechanism of Action of Clodronate: Inhibition of Mitochondrial ADP/ATP Translocase by a Nonhydrolyzable, Adenine-Containing Metabolite

et al. 2002

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Bisphosphonates are currently the most important class of antiresorptive drugs used for the treatment of diseases with excess bone resorption. Recent studies have shown that bisphosphonates can be divided into two groups with distinct molecular mechanisms of action depending on the nature of the R 2 side chain. Alendronate, like other nitrogen-containing bisphosphonates, inhibits bone resorption and causes apoptosis of osteoclasts and other cells in vitro by preventing post-translational modification of GTP-binding proteins with isoprenoid lipids. Clodronate, a bisphosphonate that lacks a nitrogen, does not inhibit protein isoprenylation but can be metabolized intracellularly to a ␤-␥-methylene (AppCp-type) analog of ATP, which is cytotoxic to macrophages in vitro. The detailed molecular basis for the cytotoxic effects of adenosine-5Ј-[␤,␥-dichloromethylene]triphosphate (AppCCl 2 p) has not been determined yet. We addressed this question by studying the effects of alendronate, clodronate, and the clodronate metabolite AppCCl 2 p on isolated mitochondria, mitochondrial fractions, and mitochondrial membrane potential in isolated human osteoclasts. We found that AppCCl 2 p inhibits mitochondrial oxygen consumption by a mechanism that involves competitive inhibition of the ADP/ATP translocase. Alendronate or the native form of clodronate did not have any immediate effect on mitochondria. However, longer treatment with liposome-encapsulated clodronate caused collapse of the mitochondrial membrane potential, although prominent apoptosis was a late event. Hence, inhibition of the ADP/ATP translocase by the metabolite AppCCl 2 p is a likely route by which clodronate causes osteoclast apoptosis and inhibits bone resorption.

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“…Recent reports have demonstrated, that FFA stimulate large‐amplitude swelling of mitochondria, preloaded with Ca 2+ and suspended in neutral medium (pH 7.2–7.4), by the opening of the permeability transition pore complex (PTP) [20–28]. In the present paper we studied large‐amplitude swelling initiated in mitochondria by Myr in alkaline KCl medium.…”

Section: Discussionmentioning

confidence: 91%

Activation of ion‐conducting pathways in the inner mitochondrial membrane – an unrecognized activity of fatty acid?

et al. 2001

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The effect of non-esterified myristate (C14:0) or dodecyl sulfate was studied on passive swelling of rat liver mitochondria suspended in hypotonic alkaline KCl medium in the absence of the potassium ionophore valinomycin. Both compounds rapidly initiated large-amplitude swelling. However, they failed to initiate swelling when the mitochondria were suspended in hypotonic alkaline sucrose medium. In contrast to myristate or dodecyl sulfate, the non-ionic detergent Triton X-100 initiated swelling of mitochondria in both of the media. The following findings indicate that the inner mitochondrial membrane (IMM) is permeabilized by myristate to K + and Cl 3 in a specific manner. (i) Swelling initiated by myristate did not respond to cyclosporin A, (ii) the protonophoric uncoupler FCCP was unable to mimic the myristate effect on swelling, and (iii) myristate-induced Cl 3 -permeation (measured with KCl medium plus valinomycin) was inhibited by N,NP P-dicyclohexylcarbodiimide, quinine or ATP. Myristate-or dodecyl sulfate-initiated swelling was paralleled by the lowering of endogenous Mg 2+ content. Both effects, stimulation of swelling and depletion of endogenous Mg 2+ are correlated with each other. Similar effects have been reported previously for the carboxylic divalent cation ionophore calcimycin (A23187). The A23187-induced swelling has identical inhibiting characteristics on Cl 3 -permeation with respect to N,NP P-dicyclohexylcarbodiimide, quinine and ATP as the myristate-stimulated swelling. Therefore, we conclude that nonesterified fatty acids increase the permeability of mitochondria to K + and Cl 3 at alkaline pH by activating Mg 2+ -dependent ionconducting pathways in IMM. ß

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Carboxyatractyloside increases the effect of oleate on mitochondrial permeability transition

Cited by 19 publications

References 28 publications

The Effect of N-Ethylmaleimide on Permeability Transition as Induced by Carboxyatractyloside, Agaric Acid, and Oleate

The Effect of N-Ethylmaleimide on Permeability Transition as Induced by Carboxyatractyloside, Agaric Acid, and Oleate

Further Insight into Mechanism of Action of Clodronate: Inhibition of Mitochondrial ADP/ATP Translocase by a Nonhydrolyzable, Adenine-Containing Metabolite

Activation of ion‐conducting pathways in the inner mitochondrial membrane – an unrecognized activity of fatty acid?

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