On the mechanism of mitochondrial permeability transition induction by glycyrrhetinic acid

Fiore, Cristina; Salvi, Mauro; Palermo, Mario; Sinigaglia, Giulietta; Armanini, Decio; Toninello, Antonio

doi:10.1016/j.bbabio.2004.05.012

Cited by 64 publications

(46 citation statements)

References 20 publications

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“…in the presence of large amounts of ROS, catalase becomes the most important scavenger of H 2 O 2 in the cytosol. These conditions may be even more serious in mitochondria, as also observed in "in vitro" investigations with the organelle treated with monoamines (7), flavones (8), isoflavones (9), and cyclic triterpenes (10,11). By interacting with transition metals of the respiratory chain, these compounds produce H 2 O 2 and the highly toxic hydroxyl radical.…”

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confidence: 98%

Catalase Takes Part in Rat Liver Mitochondria Oxidative Stress Defense

Salvi

Battaglia

Brunati

et al. 2007

Journal of Biological Chemistry

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196

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Highly purified rat liver mitochondria (RLM) when exposed to tert-butylhydroperoxide undergo matrix swelling, membrane potential collapse, and oxidation of glutathione and pyridine nucleotides, all events attributable to the induction of mitochondrial permeability transition. Instead, RLM, if treated with the same or higher amounts of H 2 O 2 or tyramine, are insensitive or only partially sensitive, respectively, to mitochondrial permeability transition. In addition, the block of respiration by antimycin A added to RLM respiring in state 4 conditions, or the addition of H 2 O 2 , results in O 2 generation, which is blocked by the catalase inhibitors aminotriazole or KCN. In this regard, H 2 O 2 decomposition yields molecular oxygen in a 2:1 stoichiometry, consistent with a catalatic mechanism with a rate constant of 0.0346 s ؊1 . The rate of H 2 O 2 consumption is not influenced by respiratory substrates, succinate or glutamate-malate, nor by N-ethylmaleimide, suggesting that cytochrome c oxidase and the glutathione-glutathione peroxidase system are not significantly involved in this process. Instead, H 2 O 2 consumption is considerably inhibited by KCN or aminotriazole, indicating activity by a hemoprotein. All these observations are compatible with the presence of endogenous heme-containing catalase with an activity of 825 ؎ 15 units, which contributes to mitochondrial protection against endogenous or exogenous H 2 O 2 . Mitochondrial catalase in liver most probably represents regulatory control of bioenergetic metabolism, but it may also be proposed for new therapeutic strategies against liver diseases. The constitutive presence of catalase inside mitochondria is demonstrated by several methodological approaches as follows: biochemical fractionating, proteinase K sensitivity, and immunogold electron microscopy on isolated RLM and whole rat liver tissue.Many human diseases, including cancer and other pathologies associated with aging, such as arteriosclerosis and cataracts, are related to mitochondrial dysfunctions provoked by reactive oxygen species (ROS) 2 (1). In this regard, the so-called free radical theory of aging has been proposed (2). ROS are highly reactive and may be extremely toxic in biological systems, as they attack a variety of molecules, including proteins, polyunsaturated lipids, and nucleic acid (3), causing the cell to die by apoptosis or necrosis. In physiological conditions, 1-2% of molecular oxygen consumption during mitochondrial respiration undergoes incomplete reduction by single electrons to form superoxide anion (O 2 . ) at the level of NADH-ubiquinone reductase (complex I) and ubiquinol-cytochrome c reductase (complex III). These two segments of the respiratory chain generate the superoxide radical by autoxidation of reduced flavin and by transferring an electron from reduced ubisemiquinone to molecular oxygen, respectively (4). Superoxide is rapidly converted to hydrogen peroxide by mitochondrial superoxide dismutase, which then produces the highly reactive hydroxyl radical (OH ⅐ ...

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mentioning

confidence: 98%

Catalase Takes Part in Rat Liver Mitochondria Oxidative Stress Defense

Salvi

Battaglia

Brunati

et al. 2007

Journal of Biological Chemistry

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196

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“…Both 18␤-GA and Cbx have been shown to affect mitochondrial function by inducing the opening of the mitochondrial permeability transition pore (PTP) in rat liver mitochondria (RLM), resulting in matrix swelling, collapse of the membrane potential, and release of cytochrome c. Cyclosporine A (CsA) abolished these effects of Cbx, including reactive oxygen species (ROS) formation, indicating that Cbx induces PTP opening through the generation of oxidative stress (16,36,37). The authors suggested that the mechanism of Cbx-activated PTP opening is oxidative stress, which is produced by interacting with the mitochondrial respiratory chain at the level of complex I and complex III (36,37).…”

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confidence: 99%

Calcium-induced permeability transition in rat brain mitochondria is promoted by carbenoxolone through targeting connexin43

Azarashvili

Baburina

Grachev

et al. 2011

American Journal of Physiology-Cell Physiology

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“…Glycyrrhizin was shown to have anti-inflammatory properties as demonstrated by decreased production of reactive oxygen species (ROS) in human neutrophils (13). GRA can induce cell death in some tumor cells, such as primary effusion lymphoma cells transformed by Kaposi sarcoma-associated herpesvirus, possibly through the release of mitochondrial apoptotic factors (14)(15)(16). Additionally, licorice flavonoids were shown to increase the susceptibility of MRSA strains to oxacillin, a ␤-lactam antibiotic (17).…”

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confidence: 99%

18β-Glycyrrhetinic Acid Inhibits Methicillin-Resistant Staphylococcus aureus Survival and Attenuates Virulence Gene Expression

Long

Mead

Hendricks

et al. 2013

Antimicrob Agents Chemother

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Methicillin-resistant Staphylococcus aureus (MRSA) has become a major source of infection in hospitals and in the community. Increasing antibiotic resistance in S. aureus strains has created a need for alternative therapies to treat disease. A component of the licorice root Glycyrrhiza spp., 18␤-glycyrrhetinic acid (GRA), has been shown to have antiviral, antitumor, and antibacterial activity. This investigation explores the in vitro and in vivo effects of GRA on MRSA pulsed-field gel electrophoresis (PFGE) type USA300. GRA exhibited bactericidal activity at concentrations exceeding 0.223 M. Upon exposure of S. aureus to sublytic concentrations of GRA, we observed a reduction in expression of key virulence genes, including saeR and hla. In murine models of skin and soft tissue infection, topical GRA treatment significantly reduced skin lesion size and decreased the expression of saeR and hla genes. Our investigation demonstrates that at high concentrations GRA is bactericidal to MRSA and at sublethal doses it reduces virulence gene expression in S. aureus both in vitro and in vivo.

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On the mechanism of mitochondrial permeability transition induction by glycyrrhetinic acid

Cited by 64 publications

References 20 publications

Catalase Takes Part in Rat Liver Mitochondria Oxidative Stress Defense

Catalase Takes Part in Rat Liver Mitochondria Oxidative Stress Defense

Calcium-induced permeability transition in rat brain mitochondria is promoted by carbenoxolone through targeting connexin43

18β-Glycyrrhetinic Acid Inhibits Methicillin-Resistant Staphylococcus aureus Survival and Attenuates Virulence Gene Expression

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