Agmatine prevents the Ca2+-dependent induction of permeability transition in rat brain mitochondria

Battaglia, Valentina; Grancara, Silvia; Satriano, Joseph; Saccoccio, Stefania; Agostinelli, Enzo; Toninello, Antonio

doi:10.1007/s00726-009-0402-0

Cited by 50 publications

(24 citation statements)

References 32 publications

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“…It should also be noted Ca 2? alone produces a significant amount of hydrogen peroxide, as previously reported in the literature (Grijalba et al 1999;Battaglia et al 2010), whereas melatonin alone does not cause any production of ROS. A very recent paper reporting the induction of ROS production by melatonin in isolated mitochondria from human mesangial cells and mice kidney tissues is in agreement with our data (Zhang et al 2011).…”

Section: Resultssupporting

confidence: 80%

Interactions of melatonin with mammalian mitochondria. Reducer of energy capacity and amplifier of permeability transition

et al. 2011

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Melatonin, a metabolic product of the amino acid tryptophan, induces a dose-dependent energy drop correlated with a decrease in the oxidative phosphorylation process in isolated rat liver mitochondria. This effect involves a gradual decrease in the respiratory control index and significant alterations in the state 4/state 3 transition of membrane potential (DW). Melatonin, alone, does not affect the insulating properties of the inner membrane but, in the presence of supraphysiological Ca 2? , induces a DW drop and colloid-osmotic mitochondrial swelling. These events are sensitive to cyclosporin A and the inhibitors of Ca 2? transport, indicative of the induction or amplification of the mitochondrial permeability transition. This phenomenon is triggered by oxidative stress induced by melatonin and Ca 2? , with the generation of hydrogen peroxide and the consequent oxidation of sulfydryl groups, glutathione and pyridine nucleotides. In addition, melatonin, again in the presence of Ca 2? , can also induce substantial release of cytochrome C and AIF (apoptosis-inducing factor), thus revealing its potential as a pro-apoptotic agent.

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Section: Resultssupporting

confidence: 80%

Interactions of melatonin with mammalian mitochondria. Reducer of energy capacity and amplifier of permeability transition

et al. 2011

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“…Agmatine protects systemic organs, especially against oxidative stress. Additionally, it shows cardioprotective and renoprotective effects on ischemic insult [36, 37], and it directly protects mitochondria from ROS [38, 39]. In the CNS, agmatine shows neuroprotective effects on various neuronal injuries: reduces the infarct size and edema after cerebral ischemia [17, 18, 40], attenuates brain damage and reactive gliosis caused by trauma [41, 42], and also decreases traumatic/ischemic spinal cord injuries [43, 44].…”

Section: Discussionmentioning

confidence: 99%

Retroviral expression of human arginine decarboxylase reduces oxidative stress injury in mouse cortical astrocytes

et al. 2014

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BackgroundIn physiologic and pathologic conditions of the central nervous system (CNS), astrocytes are a double-edged sword. They not only support neuronal homeostasis but also contribute to increases in neuronal demise. A large body of experimental evidence has shown that impaired astrocytes play crucial roles in the pathologic process of cerebral ischemia; therefore, astrocytes may represent a breakthrough target for neuroprotective therapeutic strategies. Agmatine, an endogenous polyamine catalyzed from L-arginine by arginine decarboxylase (ADC), is a neuromodulator and it protects neurons/glia against various injuries.ResultsIn this investigation, agmatine-producing mouse cortical astrocytes were developed through transduction of the human ADC gene. Cells were exposed to oxygen-glucose deprivation (OGD) and restored to a normoxic glucose-supplied condition. Intracellular levels of agmatine were measured by high performance liquid chromatography. Cell viability was evaluated by Hoechest/propidium iodide nuclear staining and lactate dehydrogenase assay. Expression of inducible nitric oxide synthase (iNOS) and matrix metalloproteinase s (MMPs) were assessed by a reverse transcription polymerase chain reaction, Western immunoblots, and immunofluorescence. We confirmed that ADC gene-expressed astrocytes produce a great amount of agmatine. These cells were highly resistant to not only OGD but also restoration, which mimicked ischemia-reperfusion injury in vivo. The neuroprotective effects of ADC seemed to be related to its ability to attenuate expression of iNOS and MMPs.ConclusionOur findings imply that astrocytes can be reinforced against oxidative stress by endogenous agmatine production through ADC gene transduction. The results of this study provide new insights that may lead to novel therapeutic approaches to reduce cerebral ischemic injuries.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2202-15-99) contains supplementary material, which is available to authorized users.

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“…Differences can occur depending on the organ of origin. For example, the biogenic amine agmatine is able to protect brain and kidney MPT (Arndt et al 2009;Battaglia et al 2010), but exhibits a concentration-dependent biphasic effect in rat liver mitochondria (RLM). At low concentrations (10-100 lM), in fact, it induces the MPT by means of increased oxidative stress caused by reactive oxygen species (ROS) produced as a by-product of agmatine catabolism (Battaglia et al 2007).…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial oxidative stress induced by Ca2+ and monoamines: different behaviour of liver and brain mitochondria in undergoing permeability transition

et al. 2011

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Mitochondrial permeability transition (MPT) is correlated with the opening of a nonspecific pore, the socalled transition pore, that triggers bidirectional traffic of inorganic solutes and metabolites across the mitochondrial membrane. This phenomenon is caused by supraphysiological Ca 2? concentrations and by other compounds leading to oxidative stress, while cyclosporin A, ADP, bongkrekic acid, antioxidant agents and naturally occurring polyamines strongly inhibit it. The effects of polyamines, including the diamine agmatine, have been widely studied in several types of mitochondria. The effects of monoamines on MPT have to date, been less well-studied, even if they are involved in a variety of neurological and neuroendocrine processes. This study shows that in rat liver mitochondria (RLM), monoamines such as tyramine, serotonin and dopamine amplify the swelling induced by calcium, and increase the oxidation of thiol groups and the production of hydrogen peroxide, effects that are counteracted by the above-mentioned inhibitors. In rat brain mitochondria (RBM), the monoamines do not amplify calcium-induced swelling, even if they demonstrate increases in the extent of oxidation of thiol groups and hydrogen peroxide production. In these mitochondria, the antioxidants are not at all or scarcely effective in suppressing mitochondrial swelling. In conclusion, we hypothesize that different mechanisms induce the MPT in the two different types of mitochondria evaluated. Calcium and monoamines induce oxidative stress in RLM, which in turn appears to induce and amplify MPT. This process is not apparent in RBM, where MPT seems resistant to oxidative stress.

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Agmatine prevents the Ca2+-dependent induction of permeability transition in rat brain mitochondria

Cited by 50 publications

References 32 publications

Interactions of melatonin with mammalian mitochondria. Reducer of energy capacity and amplifier of permeability transition

Interactions of melatonin with mammalian mitochondria. Reducer of energy capacity and amplifier of permeability transition

Retroviral expression of human arginine decarboxylase reduces oxidative stress injury in mouse cortical astrocytes

Mitochondrial oxidative stress induced by Ca2+ and monoamines: different behaviour of liver and brain mitochondria in undergoing permeability transition

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