Contribution of the mitochondrial permeability transition to lethal injury after exposure of hepatocytes to <i>t</i>-butylhydroperoxide

Nieminen, Anna‐Liisa; Saylor, A K; Tesfai, Samuel A.; Herman, Brian; Lemasters, John J.

doi:10.1042/bj3070099

Cited by 374 publications

(272 citation statements)

References 35 publications

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“…copy to disting,.,:s~-, mitochondrial from cytosolic fluorescence, since the thickness of our confocal sections (0.8-0.9 pro) is only slightly less than the diameter of a cardiac myocyte mitochondrion. In hepatocytes, Nieminen and co-workers [32] developed an approach to load calcein, a fluorescent marker, almost exclusively into the cytosol. Confocal microscopy of such calcein-labeled hepatocytes showed mitochondria as dark voids in a background of diffuse bright cytosolic fluorescence.…”

Section: Resultsmentioning

confidence: 99%

Mitochondrial free calcium transients during excitation‐contraction coupling in rabbit cardiac myocytes

et al. 1996

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Mitochondrlal free Ca 2+ may regulate mitochondrial ATP production during cardiac exercise. Here, using laser scanning confocal microscopy of adult rabbit cardiac myocytes co-loaded with Flue-3 to measure free Ca 2+ and tetramethylrhodamine methylester to identify mitochondria, we measured ! 2+ cytosolic and mitochondrla Ca transients during the contractile cycle. In resting cells, cytosolle and mitochondrlal Fiu,r~.3 signals were similar. During electrical pacing, transients of Flue-3 fluorescence occurred in both the cytosolic and mitochondrlal compartments. Both the mitochondrlal~ and the cytosollc transients were potentiated by isoproterenol. These experiments show directly that mitochondrlal free Ca 2+ rises and falls during excitation-contraction coupling in cardiac myocytes an6 that changes of mitochondrlal Ca z+ are kinetically competent to regulate mitochondrlal metabolism on a beat-to-beat basis.

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Section: Resultsmentioning

confidence: 99%

Mitochondrial free calcium transients during excitation‐contraction coupling in rabbit cardiac myocytes

et al. 1996

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“…Moreover, the MPT possesses at least two redox-sensitive sites, one of them in equilibrium with GSH of mitochondrial matrix and another that can be directly activated by ROS [30]. Therefore, in addition to the oxidation of membrane protein sulfhydryl groups, the oxidation of both GSH and NAD(P)H of mitochondrial matrix [30], followed closely by an increase in the mitochondrial Ca 2 + and ROS generation within mitochondria (or a decreasing in their detoxification), contributes to the MPT induction, as shown by studies with several MPT inducers, including tert-butylhydroperoxide [39][40][41][42] and inorganic phosphate [31,43]. Besides the generation of ROS, NO can also act on mitochondria amplifying the signals promoting the MPT [44,45].…”

Section: Discussionmentioning

confidence: 99%

Thiol protecting agents and antioxidants inhibit the mitochondrial permeability transition promoted by etoposide: implications in the prevention of etoposide-induced apoptosis

Custódio

Cardoso

Almeida

2002

Chemico-Biological Interactions

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Etoposide (VP-16) is known to promote cell apoptosis either in cancer or in normal cells as a side effect. This fact is preceded by the induction of several mitochondrial events, including increase in Bax/Bcl-2 ratio followed by cytochrome c release and consequent activation of caspase-9 and -3, reduction of ATP levels, depolarization of membrane potential (Dc) and rupture of the outer membrane. These events are apoptotic factors essentially associated with the induction of the mitochondrial permeability transition (MPT). VP-16 has been shown to stimulate the Ca 2 + -dependent MPT induction similarly to prooxidants and to promote apoptosis by oxidative stress mechanisms, which is prevented by glutathione (GSH) and N-acetylcysteine (NAC). Therefore, the aim of this work was to study the effects of antioxidants and thiol protecting agents on MPT promoted by VP-16, (2002) 169-184 170 attempting to identify the underlying mechanisms on VP-16-induced apoptosis. The increased sensitivity of isolated mitochondria to Ca 2 + -induced swelling, Ca 2 + release, depolarization of Dc and uncoupling of respiration promoted by VP-16, which are prevented by cyclosporine A proving that VP-16 induces the MPT, are also efficiently prevented by ascorbate, the primary reductant of the phenoxyl radicals produced by VP-16. The thiol reagents GSH, dithiothreitol and N-ethylmaleimide, which have been reported to prevent the MPT induction, also protect this event promoted by VP-16. The inhibition of the VP-16-induced MPT by antioxidants agrees with the prevention of etoposide-induced apoptosis by GSH and NAC and suggests the generation of oxidant species as a potential mechanism underlying the MPT that may trigger the release of mitochondrial apoptogenic factors responsible for apoptotic cascade activation.

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“…In addition, cyclosporine A, a well-known PTP blocker [64][65][66] has no effect on MAC activity, which reinforces the notion that MAC and the PTP are independent. 29 It has been shown that trifluoperazine and propranolol prevent apoptosis in some cell lines, 67,68 and trifluoperazine and dibucaine also block mitochondrial depolarization induced by glutamate in neurons. 69 Dibucaine, trifluoperazine and propranolol also block cytochrome c release from mitochondria induced by recombinant Bax and 'BH3 domain-only' proteins like t-Bid.…”

Section: Pharmacology Of Mac/bax Channelsmentioning

confidence: 99%

Is MAC the knife that cuts cytochrome c from mitochondria during apoptosis?

2006

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Apoptosis is a phenomenon fundamental to higher eukaryotes and essential to mechanisms controlling tissue homeostasis. Bcl-2 family proteins tightly control this cell death program by regulating the permeabilization of the mitochondrial outer membrane and, hence, the release of cytochrome c and other proapoptotic factors. Mitochondrial apoptosisinduced channel (MAC) is the mitochondrial apoptosisinduced channel and is responsible for cytochrome c release early in apoptosis. MAC activity is detected by patch clamping mitochondria at the time of cytochrome c release. The Bcl-2 family proteins regulate apoptosis by controlling the formation of MAC. Depending on cell type and apoptotic inducer, Bax and/or Bak are structural component(s) of MAC. Overexpression of the antiapoptotic protein Bcl-2 eliminates MAC activity. The focus of this review is a biophysical characterization of MAC activity and its regulation by Bcl-2 family proteins, and ends with some discussion of therapeutic targets.

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Contribution of the mitochondrial permeability transition to lethal injury after exposure of hepatocytes to t-butylhydroperoxide

Cited by 374 publications

References 35 publications

Mitochondrial free calcium transients during excitation‐contraction coupling in rabbit cardiac myocytes

Mitochondrial free calcium transients during excitation‐contraction coupling in rabbit cardiac myocytes

Thiol protecting agents and antioxidants inhibit the mitochondrial permeability transition promoted by etoposide: implications in the prevention of etoposide-induced apoptosis

Is MAC the knife that cuts cytochrome c from mitochondria during apoptosis?

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