Neurodegeneration and peroxidases

Everse, Johannes; Coates, Penelope W.

doi:10.1016/j.neurobiolaging.2007.10.007

Cited by 41 publications

(46 citation statements)

References 153 publications

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“…Transitions among different conformations are regulated by endogenous molecules such as ATP and may be affected by synthetic molecules such as minocycline. Minocycline has been shown to have neuroprotective effects in animal models of neurodegenerative diseases [7,25,26]. Our findings suggest as minocycline may have a twofold effect on cyt c apoptotic role: a former effect due to its potency in avoiding or decreasing the peroxidase activity of cyt c in the early stages of apoptosis and a later effect related to its competition in cyt c-Apaf-1 binding interaction in the cytosol.…”

Section: Discussionmentioning

confidence: 66%

“…Gaining of enzymatic activity at this stage could be responsible for the oxidation of vulnerable cytosolic proteins such as a-synuclein that associates in large aggregates leading to the formation of Lewy bodies that were found in the degenerating neurons from subjects with Parkinson's disease [23]. Of particular interest is the presence of a considerable amount of immunoreactive cyt c in Lewy bodies [7]. Taken as a whole, the evidence leads us to propose that the cyt c's conversion into a peroxidase in the early events of apoptosis may play a significant role in the complex neurodegeneration scenario.…”

Section: Induction and Inhibition Of Peroxidase Activitymentioning

confidence: 99%

“…Taken as a whole, the evidence leads us to propose that the cyt c's conversion into a peroxidase in the early events of apoptosis may play a significant role in the complex neurodegeneration scenario. as it was hypothesized for a few heme-peroxidases [7] Thus it would be of relevance, relying on structural studies, to identify molecules able to regulate the peroxidase function of cyt c/CL complex and thus functioning as potential inhibitors of CL oxidation with anti-apoptotic properties. To this aim, Kagan et al recently described new approaches to mitochondrial targeting of small biologically active Table 1 Kinetics parameters of peroxidase activity of wt cyt c and ''non native'' forms.…”

Section: Induction and Inhibition Of Peroxidase Activitymentioning

confidence: 99%

“…Moreover, the peroxidase kinetic parameters of the non native conformers here investigated were measured also in the presence of minocycline, an antibiotic endowed with antioxidant properties reported to act as peroxidase inhibitor and neuroprotective agent that delays progression of neuron degeneration [7].…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Conversion of cytochrome c into a peroxidase: Inhibitory mechanisms and implication for neurodegenerative diseases

Patriarca

Polticelli

Piro

et al. 2012

Archives of Biochemistry and Biophysics

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a b s t r a c tA further function of cytochrome c (cyt c), beyond respiration, is realized outside mitochondria in the apoptotic program. In the early events of apoptosis, the interaction of cyt c with a mitochondrion-specific phospholipid, cardiolipin (CL), brings about a conformational transition of the protein and acquirement of peroxidase activity. The hallmark of cyt c with peroxidase activity is its partial unfolding accompanied by loosening of the Fe sixth axial bond and an enhanced access of the heme catalytic site to small molecules like H 2 O 2 . To investigate the peroxidase activity of non-native cyt c, different forms of the protein were analyzed with the aim to correlate their structural features with the acquired enzymatic activity and apoptogenic properties (wt cyt c/CL complex and two single cyt c variants, H26Y and Y67H, free and bound to CL). The results suggest that cyt c may respond to different environments by changing its fold thus favouring the exertion of different biological functions in different pathophysiological cell conditions. Transitions among different conformations are regulated by endogenous molecules such as ATP and may be affected by synthetic molecules such as minocycline, thus suggesting a mechanism explaining its use as therapeutic agent impacting on disease-associated oxidative and apoptotic mechanisms.

show abstract

Section: Discussionmentioning

confidence: 66%

Section: Induction and Inhibition Of Peroxidase Activitymentioning

confidence: 99%

Section: Induction and Inhibition Of Peroxidase Activitymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Conversion of cytochrome c into a peroxidase: Inhibitory mechanisms and implication for neurodegenerative diseases

Patriarca

Polticelli

Piro

et al. 2012

Archives of Biochemistry and Biophysics

View full text Add to dashboard Cite

show abstract

“…Early in apoptosis, the redox function of cyt c in the respiratory chain switches to a peroxidase function [44,45]. The increased peroxidase activity of cyt c is implicated in various neurodegenerative diseases, such as Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis (ALS) [46]. To gain a better understanding of the role of oxidized cytochrome c (Fe 3 þ cyt c) in oxidative sulfite toxicity, we have employed the powerful, sensitive, and specific technique of electron paramagnetic resonance (EPR) spin trapping technique to investigate the oxidation of sulfite and generation of free radicals by the Fe 3 þ cyt c in the absence and presence of H 2 O 2 .…”

Section: Introductionmentioning

confidence: 99%