Oxidative Stress Is Responsible for Mitochondrial Permeability Transition Induction by Salicylate in Liver Mitochondria

Battaglia, Valentina; Salvi, Mauro; Toninello, Antonio

doi:10.1074/jbc.m502391200

Cited by 74 publications

(52 citation statements)

References 51 publications

(25 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The redox state of endogenous pyridine nucleotides was followed fluorometrically in an Aminco-Bowman 4-8202 spectrofluorometer with excitation at 354 nm and emission at 462 nm. Respiratory control index and P/O ratio were calculated as reported previously (where P/O is the ratio of the number of ATP molecules formed to the number of oxygen molecules reduced by electron transport) (14). Determination of oxidation of glutathione oxidation of glutathione was performed as described by Tietze (25).…”

Section: Methodsmentioning

confidence: 99%

Catalase Takes Part in Rat Liver Mitochondria Oxidative Stress Defense

Salvi

Battaglia

Brunati

et al. 2007

Journal of Biological Chemistry

Self Cite

196

View full text Add to dashboard Cite

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 ...

show abstract

Section: Methodsmentioning

confidence: 99%

Catalase Takes Part in Rat Liver Mitochondria Oxidative Stress Defense

Salvi

Battaglia

Brunati

et al. 2007

Journal of Biological Chemistry

Self Cite

196

View full text Add to dashboard Cite

show abstract

“…Oxygen radicals are produced by mitochondria, and those produced in other cells can easily enter a target cell via the cell membrane and thereby reach the interior of mitochondria. The mechanisms by which oxygen radicals impair mitochondrial function involve mitochondrial membrane permeability transitions [16] and mitochondrial DNA damage [42] , leading to cell death. In such processes, mitochondrial and cytosolic Ca 2+ likely play important roles.…”

Section: H 2 O 2 Impairs Mitochondrial Function and Decreases Intracementioning

confidence: 99%

“…To record Fura-2 fluorescence, excitation wavelengths selected from a xenon light source were 340 and 380 nm, and the emission wavelength was 510 nm. [Ca 2+ ] i was calculated using the following formula [16] : [Ca 2+ ] i =K d β (R-R min )/(R max -R), where R is the ratio of the fluorescence intensities at the two wavelengths (F 340 /F 380 ), K d is the dissociation constant of Fura-2 binding to Ca 2+ , and β is the maximum fluorescence at 380 nm (F 380 max ) divided by the minimal fluorescence at 380 nm (F 380 min ). The values R max , R min , F 380 max , and F 380 min were obtained by calibration using ionomycin (Calbiochem, La Jolla, CA) and EGTA.…”

Section: +mentioning

confidence: 99%

“…In cardiac myocytes [15] , an inhibition of cellular Ca 2+ extrusion or uptake seems to be responsible for the elevation of [Ca 2+ ] i induced by oxygen radicals. In addition, oxygen radicals have also been shown to be responsible for Ca 2+ -dependent mitochondrial dysfunction [16] and Ca 2+ entry [17] . The Ca 2+ influx resulting from H 2 O 2 seems to involve the Fas protein [17] .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Hydrogen peroxide mobilizes Ca2+ through two distinct mechanisms in rat hepatocytes

et al. 2008

View full text Add to dashboard Cite

Aim:Hydrogen peroxide (H 2 O 2 ) is produced during liver transplantation. Ischemia/reperfusion induces oxidation and causes intracellular Ca 2+ overload, which harms liver cells. Our goal was to determine the precise mechanisms of these processes. Methods: Hepatocytes were extracted from rats. Intracellular Ca 2+ concentrations ([Ca 2+ ] i ), inner mitochondrial membrane potentials and NAD(P)H levels were measured using fluorescence imaging. Phospholipase C (PLC) activity was detected using exogenous PIP 2 . ATP concentrations were measured using the luciferin-luciferase method. Patch-clamp recordings were performed to evaluate membrane currents.

show abstract

“…Interestingly, salicylate has recently been described to evoke oxidative stress (Battaglia et al, 2005), which could account for the activation of JNK that represents a classic stress-activated protein kinase (Adler et al, 1999). To test this hypothesis, we measured the generation of reactive oxygen species as described previously (Fü rst et al, 2005).…”

Section: Induction Of Endothelial Ho-1 By Salicylate 393mentioning

confidence: 99%

Nuclear Factor-κB-Independent Anti-Inflammatory Action of Salicylate in Human Endothelial Cells: Induction of Heme Oxygenase-1 by the c-Jun N-Terminal Kinase/Activator Protein-1 Pathway

Fürst¹,

Blumenthal²,

Kiemer³

et al. 2006

J Pharmacol Exp Ther

View full text Add to dashboard Cite

In contrast to aspirin, salicylate, its active metabolite, possesses profound anti-inflammatory properties without blocking cyclooxygenase. Inhibition of the transcription factor nuclear factor-B (NF-B) has been discussed to play a role in the anti-inflammatory profile of salicylate. However, NF-B-independent effects of salicylate have been assumed but have up to now been poorly investigated. Therefore, the aim of the present study was to investigate NF-B-independent anti-inflammatory mechanisms of salicylate in human umbilical vein endothelial cells using interleukin-4 (IL-4) as NF-B-independent proinflammatory stimulus and P-selectin as inflammatory read-out parameter. Using quantitative real-time reverse transcriptionpolymerase chain reaction, we found that salicylate decreases IL-4-induced P-selectin expression. As judged by Western blot analysis, salicylate increased endothelial heme oxygenase-1 (HO-1) protein levels. Using both the HO-1 inhibitor tin(II) protoporphyrin IX and HO-1 antisense oligonucleotides, we causally linked the induction of HO-1 to the decrease of P-selectin. Moreover, we were interested in the signaling mechanisms leading to the up-regulation of HO-1 by salicylate. c-Jun NH 2 -terminal kinase (JNK) was found to be activated by salicylate, and we could causally link this activation to the induction of HO-1 by using the JNK inhibitor 1,9-pyrazoloanthrone. By applying activator protein-1 (AP-1) decoys, it was shown that the transcription factor AP-1 is crucially involved in the up-regulation of HO-1 downstream of JNK. In summary, our study introduces HO-1 as novel NF-B-independent anti-inflammatory target of salicylate in human endothelial cells. Moreover, we elucidated the JNK/AP-1 pathway as crucial for the induction of HO-1 by salicylate.

show abstract

Oxidative Stress Is Responsible for Mitochondrial Permeability Transition Induction by Salicylate in Liver Mitochondria

Cited by 74 publications

References 51 publications

Catalase Takes Part in Rat Liver Mitochondria Oxidative Stress Defense

Catalase Takes Part in Rat Liver Mitochondria Oxidative Stress Defense

Hydrogen peroxide mobilizes Ca2+ through two distinct mechanisms in rat hepatocytes

Nuclear Factor-κB-Independent Anti-Inflammatory Action of Salicylate in Human Endothelial Cells: Induction of Heme Oxygenase-1 by the c-Jun N-Terminal Kinase/Activator Protein-1 Pathway

Contact Info

Product

Resources

About