Hydrogen peroxide production by monoamine oxidase in isolated rat-brain mitochondria: its effect on glutathione levels and Ca2+ efflux

Sandri, Gabriella; Panfili, Enrico; Ernster, Lars

doi:10.1016/0304-4165(90)90092-b

Cited by 85 publications

(49 citation statements)

References 31 publications

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“…This result is in accordance with our earlier finding [10] that brain mitochondria can utilize both endogenous and externally added substrates for these enzymes. The present evidence for a differential distribution of GPx and PHGPx in relation to the mitochondrial inner membrane is of special interest, suggesting a strategic role of the two enzymes in eliminating, on one hand, HzO2 generated in the inner and outer rnitochondrial compartments by superoxide dismutase and by monoamme oxidase; and, on the other hand, phospholipid hydroperoxides formed in the inner membrane which is an important potential site of lipid peroxidation (27)(28)(29).…”

Section: Methodssupporting

confidence: 94%

Distribution of glutathione peroxidases glutathione reductase in rat brain mitochondria

1991

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The distribution of glutathione reductase (GR), gtutathione peroxidase (GPx) and phosphotipid hydroperoxide giutathione peroxidase (PHGPx) in isolated rat brain mitochondria was investigated, using a fractionation procedure for the separation of inner and outer membranes, contact sites between the two membranes and a soluble Fraction mainly originating from the mitochondrial matrix. The data indicate that GW and GPx are concentrated in the soluble fraction, with a minor portion of the two enzymes being associated with the contact sites. PHGPx is localized largely in the inner membrane. The possible functional significance of these findings is discussed.

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Section: Methodssupporting

confidence: 94%

Distribution of glutathione peroxidases glutathione reductase in rat brain mitochondria

1991

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“…Monoamine oxidase B, which was also markedly upregulated in the terminal stage of pacing-induced heart failure, was previously found overexpressed in atrial tissue of patients with atrial fibrillation (14). The authors of that study pointed out that monoamine oxidase B is involved in oxidative deamination of biologic amines and, when it metabolizes tyramine (10), it generates the oxidant H 2 O 2 that enhances the release of Ca 2ϩ and glutathione from mitochondria (26), leading to mitochondrial damage (8). Based on these premises, it is difficult to understand whether, in our dogs, monoamine oxidase B upregulation is a compensatory or a maladaptive mechanism.…”

Section: Discussionmentioning

confidence: 99%

Altered expression of a limited number of genes contributes to cardiac decompensation during chronic ventricular tachypacing in dogs

Ojaimi

Qanud

Hintze

et al. 2007

Physiological Genomics

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Ojaimi C, Qanud K, Hintze TH, Recchia FA. Altered expression of a limited number of genes contributes to cardiac decompensation during chronic ventricular tachypacing in dogs. Physiol Genomics 29: 76 -83, 2007. First published December 12, 2006; doi:10.1152/physiolgenomics.00159.2006.-Our aim was to determine the changes in the gene expression profile occurring during the transition from compensated dysfunction (CD) to decompensated heart failure (HF) in pacing-induced dilated cardiomyopathy. Twelve chronically instrumented dogs underwent left ventricular pacing at 210 beats/min for 3 wk and at 240 beats thereafter, and four normal dogs were used as control. The transition from CD to HF occurred between the 3rd and 4th wk of pacing, with end-stage HF at 28 Ϯ 1 days. RNA was extracted from left ventricular tissue at control and 3 and 4 wk of pacing (n ϭ 4) and tested with the Affymetrix Canine Array. We found 509 genes differentially expressed in CD vs. control (P Յ 0.05, fold change ՆϮ2), with 362 increasing and 147 decreasing; 526 genes were differentially expressed in HF vs. control (P Յ 0.05; fold change ՆϮ2), with 439 increasing and 87 decreasing. To better understand the transition, we compared gene alterations at 3 vs. 4 wk pacing and found that only 30 genes differed (P Յ 0.05; fold change of Ϯ2). We conclude that a number of processes including normalization of gene regulation during decompensation, appearance of new upregulated genes and maintenance of gene expression all contribute to the transition to overt heart failure with an unexpectedly small number of genes differentially regulated. heart failure; pacing dog; microarray OVER THE PAST YEARS OTHER authors and we have used chronically instrumented dogs with high-frequency cardiac pacing to study pathophysiological and molecular mechanisms related to the development of dilated cardiomyopathy. This model of congestive heart failure is characterized by a very predictable evolution and reproduces many key features of the human disease, including progressive ventricular chambers dilation and wall thinning, decreased contractility, neurohormonal activation, beta adrenergic desensitization, and altered metabolism (19). In particular, we could determine functional and metabolic changes occurring only between the 3rd and 4th wk of pacing, i.e., during the transition from compensated to decompensated failure (25). The marked cardiac functional impairment and systemic deterioration observed during this relatively short phase of transition suggests the occurrence of profound molecular alterations. Their identification would provide notable insights in the pathophysiology and clinical management of heart failure. Unfortunately, given the complexity of the heart failure syndrome, such molecular changes are likely very numerous and interrelated, while most studies have been focused on single or selected groups of molecules, due to the limitations of the classical methods of analysis.More recently, global gene transcript profiling has emerged as a powerful tool f...

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“…A proportion of the cellular Bcl-2 protein is associated with the mitochondrial outer membrane (Krajewski et al, 1993) and the clorgyline-and l-deprenyl-sensitive monoamine oxidases A and B, respectively, are similarly located. Hydrogen peroxide is a product of the oxidative deamination of amines by MAO, and this may act as a potential source of toxic reactive-oxygen radicals (see, for example, Sandri et al, 1990). Regulation of mitochondrial and/or cytosolic reactive oxygen species (ROS) levels in mammalian cells might be mediated, in part, by the bcl-2 gene product (Hockenbery et al, 1993).…”

Section: Discussionmentioning

confidence: 99%

Monoamine oxidase inhibitors l-deprenyl and clorgyline protect nonmalignant human cells from ionising radiation and chemotherapy toxicity

Seymour¹,

Mothersill²,

Mooney³

et al. 2003

Br J Cancer

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l-Deprenyl (R-(À)-deprenyl, selegiline) is an inhibitor of monoamine oxidase-B (MAO-B) that is known to protect nerve cells from a variety of chemical and physical insults. As apoptosis is a common mechanism of radiation-induced cell death, the effect of l-deprenyl on the survival of cultured cells and tissue explants was studied following exposure to gamma radiation. The results obtained were compared with the effects of the less-selective MAO-B inhibitor pargyline and the MAO-A inhibitor clorgyline. l-Deprenyl at a concentration of 10 À9 M protected the nontumorigenic cell line (HaCaT) and normal human urothelial explants from the effects of cobalt-60 gamma radiation, but did not protect tumorigenic human cell lines HaCaT-ras, HPV-transfected human keratinocytes (HPV-G cells), or PC3. Human bladder carcinoma explants were not protected. Clorgyline showed a smaller protective effect of normal cells, whereas pargyline had no effect. Radiation-induced delayed effects (genomic instability measured as delayed cell death) were prevented in normal cells by l-deprenyl but, interestingly, deprenyl appeared to increase the amount of delayed death in the tumorigenic cell lines. Studies using l-deprenyl prior to the exposure of nonmalignant cells to cisplatin showed that cell death due to this agent was also reduced. Treatment of cultures of nontumorigenic cells with l-deprenyl or clorgyline significantly increased the levels of the protein Bcl-2 following irradiation, but there was no such effect on the already-elevated levels of this protein in the tumour samples. Since the Bcl-2 has been shown to be an inhibitor of apoptosis or programmed cell death, this would imply that the protective effects of l-deprenyl and clorgyline involve activation of antiapoptotic pathways within the normal cell. This hypothesis is supported by data showing reduced levels of apoptosis in HaCAT cells and in normal bladder explant cultures following treatment with l-deprenyl.

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Hydrogen peroxide production by monoamine oxidase in isolated rat-brain mitochondria: its effect on glutathione levels and Ca2+ efflux

Cited by 85 publications

References 31 publications

Distribution of glutathione peroxidases glutathione reductase in rat brain mitochondria

Distribution of glutathione peroxidases glutathione reductase in rat brain mitochondria

Altered expression of a limited number of genes contributes to cardiac decompensation during chronic ventricular tachypacing in dogs

Monoamine oxidase inhibitors l-deprenyl and clorgyline protect nonmalignant human cells from ionising radiation and chemotherapy toxicity

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