Manganic Porphyrins Possess Catalase Activity and Protect Endothelial Cells against Hydrogen Peroxide-Mediated Injury

Day, Brian J.; Fridovich, Irwin; Crapo, James D.

doi:10.1006/abbi.1997.0341

Cited by 278 publications

(197 citation statements)

References 37 publications

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“…To confirm that the Cu toxicity in our primary neuronal cultures was mediated by free radicals and was not an unrelated effect, cultures were exposed to Cu in the presence of the free radical scavenger MnTMPyP (Day et al, 1997) These data suggest that a loss of neuronal GSH homeostasis results in significant exacerbation of Cu toxicity through a decrease in free radical detoxification.…”

Section: Mntmpyp a Free Radical Scavenger Inhibits Toxicity Inducedmentioning

confidence: 75%

“…This is supported by studies showing GSH to be important for cellular Cu transport, detoxification, and sequestration to metalloproteins and to the important antioxidant enzyme CuIZn SOD (Freedman et al, 1989;Ferreira et al, 1993;Vulpe and Packman, 1995). The role of free radicals in Cu toxicity was confirmed by abolition of toxicity using the H,O, and 0,-scavenger MnTMPyP (Day et al, 1997). The depletion of GSH by BSO can also result in a significant increase in cellular Cu (11) uptake (Tong and McArdle, 1995).…”

Section: Discussionmentioning

confidence: 92%

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Exacerbation of Copper Toxicity in Primary Neuronal Cultures Depleted of Cellular Glutathione

White

Bush

Beyreuther

et al. 1999

Journal of Neurochemistry

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Perturbations to glutathione (GSH) metabolism may play an important role in neurodegenerative disorders such as Alzheimer's, Parkinson's, and prion diseases. A primary function of GSH is to prevent the toxic interaction between free radicals and reactive transition metals such as copper (Cu). Due to the potential role of Cu in neurodegeneration, we examined the effect of GSH depletion on Cu toxicity in murine primary neuronal cultures. Depletion of cellular GSH with L-buthionine-[S,R]-sulfoximine resulted in a dramatic potentiation of Cu toxicity in neurons without effect on iron (Fe) toxicity. Similarly, inhibition of glutathione reductase (GR) activity with 1,3-bis(2-chloroethyl)-l -nitrosurea also increased Cu toxicity in neurons. To determine if the Alzheimer's amyloid-p (Ap) peptide can affect neuronal resistance to transition metal toxicity, we exposed cultures to nontoxic concentrations of Ap25-35 in the presence or absence of Cu or Fe. Ap25-35 pretreatment was found to deplete neuronal GSH and increase GR activity, confirming the ability of Ap to perturb neuronal GSH homeostasis.Ap25-35 pretreatment potently increased Cu toxicity but had no effect on Fe toxicity. These studies demonstrate an important role for neuronal GSH homeostasis in selective protection against Cu toxicity, a finding with widespread implications for neurodegenerative disorders.

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Section: Mntmpyp a Free Radical Scavenger Inhibits Toxicity Inducedmentioning

confidence: 75%

Section: Discussionmentioning

confidence: 92%

Exacerbation of Copper Toxicity in Primary Neuronal Cultures Depleted of Cellular Glutathione

White

Bush

Beyreuther

et al. 1999

Journal of Neurochemistry

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“…In addition, the chemical properties of the cysteinyl thiol of NAC provide antioxidant properties (34). MnTBAP, a stable metalloporphyrin that is a cell-permeable low molecular weight superoxide dismutase mimetic and peroxynitrite scavenger (35), also has the capability to scavenge H 2 O 2 in certain cell types (36).…”

Section: Potassium Antimony Tartrate Is Cytotoxic To L Donovanimentioning

confidence: 99%

Antimonial-induced Increase in Intracellular Ca2+ through Non-selective Cation Channels in the Host and the Parasite Is Responsible for Apoptosis of Intracellular Leishmania donovani Amastigotes

Sudhandiran

Shaha

2003

Journal of Biological Chemistry

154

126

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The capability of the obligate intracellular parasites like Leishmania donovani to survive within the host cell parasitophorous vacuoles as nonmotile amastigotes determines disease pathogenesis, but the mechanism of elimination of the parasites from these vacuoles are not well understood. By using the anti-leishmanial drug potassium antimony tartrate, we demonstrate that, upon drug exposure, intracellular L. donovani amastigotes undergo apoptotic death characterized by nuclear DNA fragmentation and externalization of phosphatidylserine. Changes upstream of DNA fragmentation included generation of reactive oxygen species like superoxide, nitric oxide, and hydrogen peroxide that were primarily concentrated in the parasitophorous vacuoles. In the presence of antioxidants like N-acetylcysteine or Mn(III) tetrakis(4-benzoic acid)porphyrin chloride, an inhibitor of inducible nitric-oxide synthase, a diminution of reactive oxygen species generation and improvement of amastigote survival were observed, suggesting a close link between drug-induced oxidative stress and amastigote death. Changes downstream to reactive oxygen species increase involved elevation of intracellular Ca 2؉ concentrations in both the parasite and the host that was preventable by antioxidants. Flufenamic acid, a non-selective cation channel blocker, decreased the elevation of Ca 2؉ in both the cell types and reduced amastigote death, thus establishing a central role of Ca 2؉ in intracellular parasite clearance. This influx of Ca 2؉ was preceded by a fall in the amastigote mitochondrial membrane potential. Therefore, this study projects the importance of flufenamic acid-sensitive non-selective cation channels as important modulators of antimonial efficacy and lends credence to the suggestion that, within the host cell, apoptosis is the preferred mode of death for the parasites.

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“…41) In particular, much attention has been paid to metalloporphyrins, which demonstrated higher stability in the presence of metal chelators than other metal complexes. 41,42) A few metalloporphyrins have shown the prominent ability to catalyze the dismutation of superoxide and to protect mammalian cells and SOD-deficient strains against intracellular superoxide-mediated injury. 8,38,43) FeCe6, a derivative of porphyrin, also exhibited SOD-like activity in a very limited number of reports, 20,21) and prevented the injury associated with ROS in mammalian model systems.…”

Section: Discussionmentioning

confidence: 99%

“…It was proposed that catalase activity of some manganic porphyrins might be responsible for their protective effect against H 2 O 2 -induced endothelial cell injury. 42) On the other hand, nicergoline, an ergoline derivative, protected mammalian cells from H 2 O 2 by up-regulation of intracellular catalase. 48) However, FeCe6 showed negligible H 2 O 2 scavenging activity by in vitro catalase assay and it did not affect intracellular catalase or SOD activity after 10 h incubation of 100 mM FeCe6 to human endothelial cells (data not shown).…”

Section: Discussionmentioning

confidence: 99%

Iron Chlorin e6 Scavenges Hydroxyl Radical and Protects Human Endothelial Cells against Hydrogen Peroxide Toxicity.

Yoon

Yang

2001

Biological & Pharmaceutical Bulletin

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Manganic Porphyrins Possess Catalase Activity and Protect Endothelial Cells against Hydrogen Peroxide-Mediated Injury

Cited by 278 publications

References 37 publications

Exacerbation of Copper Toxicity in Primary Neuronal Cultures Depleted of Cellular Glutathione

Exacerbation of Copper Toxicity in Primary Neuronal Cultures Depleted of Cellular Glutathione

Antimonial-induced Increase in Intracellular Ca2+ through Non-selective Cation Channels in the Host and the Parasite Is Responsible for Apoptosis of Intracellular Leishmania donovani Amastigotes

Iron Chlorin e6 Scavenges Hydroxyl Radical and Protects Human Endothelial Cells against Hydrogen Peroxide Toxicity.

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