Are reactive oxygen species involved in Alzheimer's disease?

Benzi, G.; Moretti, Antonio

doi:10.1016/0197-4580(95)00066-n

Cited by 333 publications

(162 citation statements)

References 173 publications

Supporting

Mentioning

160

Contrasting

Unclassified

Order By: Relevance

“…[278]) and upon ' aging ' of the materials make one wary of these data, as do the detailed characteristics of the EPR spectra. Regardless of this problem, radical metabolism [280] and protein oxidation could lead either to cross-linking and aggregation of proteins into tangles or to cytotoxic signals that alter ion transporters and neurotransmission [281], and in these ways may contribute specifically to the progression of Alzheimer's disease.…”

Section: Neurodegenerative Diseasesmentioning

confidence: 99%

Biochemistry and pathology of radical-mediated protein oxidation

Dean

Stocker

et al. 1997

Biochemical Journal

1,535

982

View full text Add to dashboard Cite

Radical-mediated damage to proteins may be initiated by electron leakage, metal-ion-dependent reactions and autoxidation of lipids and sugars. The consequent protein oxidation is O2-dependent, and involves several propagating radicals, notably alkoxyl radicals. Its products include several categories of reactive species, and a range of stable products whose chemistry is currently being elucidated. Among the reactive products, protein hydroperoxides can generate further radical fluxes on reaction with transition-metal ions; protein-bound reductants (notably dopa) can reduce transition-metal ions and thereby facilitate their reaction with hydroperoxides; and aldehydes may participate in Schiff-base formation and other reactions. Cells can detoxify some of the reactive species, e.g. by reducing protein hydroperoxides to unreactive hydroxides. Oxidized proteins are often functionally inactive and their unfolding is associated with enhanced susceptibility to proteinases. Thus cells can generally remove oxidized proteins by proteolysis. However, certain oxidized proteins are poorly handled by cells, and together with possible alterations in the rate of production of oxidized proteins, this may contribute to the observed accumulation and damaging actions of oxidized proteins during aging and in pathologies such as diabetes, atherosclerosis and neurodegenerative diseases. Protein oxidation may also sometimes play controlling roles in cellular remodelling and cell growth. Proteins are also key targets in defensive cytolysis and in inflammatory self-damage. The possibility of selective protection against protein oxidation (antioxidation) is raised.

show abstract

Section: Neurodegenerative Diseasesmentioning

confidence: 99%

Biochemistry and pathology of radical-mediated protein oxidation

Dean

Stocker

et al. 1997

Biochemical Journal

1,535

982

View full text Add to dashboard Cite

show abstract

“…ROS have been implicated in apoptosis, cellular injury during ischemia and reperfusion, and the aging process as well as in the pathophysiology of several neurodegenerative diseases including Parkinson, Huntington, and Alzheimer diseases (2,3). More recently, it has been recognized that ROS from mitochondrial sources is also involved in cellular signaling (4).…”

mentioning

confidence: 99%

“…The mitochondrial respiratory chain is not only the main source of ATP in eukaryotic cells, but it is also responsible for the production of deleterious reactive oxygen species (ROS) 2 (1). ROS have been implicated in apoptosis, cellular injury during ischemia and reperfusion, and the aging process as well as in the pathophysiology of several neurodegenerative diseases including Parkinson, Huntington, and Alzheimer diseases (2,3).…”

mentioning

confidence: 99%

The Mechanism of Mitochondrial Superoxide Production by the Cytochrome bc1 Complex

Dröse

Brandt

2008

Journal of Biological Chemistry

325

234

View full text Add to dashboard Cite

Production of reactive oxygen species (ROS) by the mitochondrial respiratory chain is considered to be one of the major causes of degenerative processes associated with oxidative stress. Mitochondrial ROS has also been shown to be involved in cellular signaling. It is generally assumed that ubisemiquinone formed at the ubiquinol oxidation center of the cytochrome bc 1 complex is one of two sources of electrons for superoxide formation in mitochondria. Here we show that superoxide formation at the ubiquinol oxidation center of the membrane-bound or purified cytochrome bc 1 complex is stimulated by the presence of oxidized ubiquinone indicating that in a reverse reaction the electron is transferred onto oxygen from reduced cytochrome b L via ubiquinone rather than during the forward ubiquinone cycle reaction. In fact, from mechanistic studies it seems unlikely that during normal catalysis the ubisemiquinone intermediate reaches significant occupancies at the ubiquinol oxidation site. We conclude that cytochrome bc 1 complexlinked ROS production is primarily promoted by a partially oxidized rather than by a fully reduced ubiquinone pool. The resulting mechanism of ROS production offers a straightforward explanation of how the redox state of the ubiquinone pool could play a central role in mitochondrial redox signaling.The mitochondrial respiratory chain is not only the main source of ATP in eukaryotic cells, but it is also responsible for the production of deleterious reactive oxygen species (ROS) 2 (1). ROS have been implicated in apoptosis, cellular injury during ischemia and reperfusion, and the aging process as well as in the pathophysiology of several neurodegenerative diseases including Parkinson, Huntington, and Alzheimer diseases (2, 3). More recently, it has been recognized that ROS from mitochondrial sources is also involved in cellular signaling (4). Within the respiratory chain, complex I (NADH:ubiquinone oxidoreductase) and the cytochrome bc 1 complex (complex III, ubiquinol:cytochrome c oxidoreductase) were identified as the main sources of superoxide anion radicals (O 2 . ; Fig. 1). In complex I, superoxide was shown to be produced primarily by the oxidation of reduced flavine or flavine semiquinone (5, 6). It has been shown a long time ago (7, 8) that superoxide is formed at the ubiquinol oxidation center (Q o site, center P) of the cytochrome bc 1 complex. The rate of superoxide formation is strongly increased under conditions of so-called oxidant-induced reduction, i.e. in the presence of the specific center N inhibitor antimycin A, sufficient amounts of reducing equivalents, and an oxidized downstream respiratory chain. According to the general scheme of the protonmotive Q cycle operating in the cytochrome bc 1 complex, ubisemiquinone is formed during ubiquinol oxidation (9). However, more recent mechanistic studies aimed at understanding the strict control of the Q cycle suggest that the bifurcated ubiquinol oxidation at center P occurs in a quasiconcerted reaction (10 -13). In fact, formation...

show abstract

“…[2][3][4] Normally, the amount of ROS is maintained at the basal and nontoxic level via the regulation of the antioxidant defense system of cells. Excess ROS, the so-called oxidative stress, can lead to cell damage and apoptosis [5][6][7][8] and is found to be related to the development of certain diseases such as Parkinson's disease, [9][10][11][12] Alzheimer's disease, [13][14][15] atherosclerosis, [16][17][18] and heart failure. [19][20][21] Especially, it has long been suggested that ROS are critically involved in cancer cell functions.…”

Section: Introductionmentioning

confidence: 99%

Effects of shear stresses and antioxidant concentrations on the production of reactive oxygen species in lung cancer cells

Zhu

Tsai

et al. 2013

Biomicrofluidics

View full text Add to dashboard Cite

Reactive oxygen species (ROS) are known to be a key factor in the development of cancer, and many exogenous sources are supposed to be related to the formation of ROS. In this paper, a microfluidic chip was developed for studying the production of ROS in lung cancer cells under different chemical and physical stimuli. This chip has two unique features: (1) five relative concentrations of 0, 1/8, 1/2, 7/8, and 1 are achieved in the culture regions; (2) a shear stress gradient is produced inside each of the five culture areas. Lung cancer cells were seeded inside this biocompatible chip for investigating their response to different concentrations of H 2 O 2 , a chemical stimulus known to increase the production of ROS. Then the effect of shear stress, a physical stimulus, on lung cancer cells was examined, showing that the production of ROS was increased in response to a larger shear stress. Finally, two antioxidants, a-tocopherol and ferulic acid, were used to study their effects on reducing ROS. It was found that high-dose a-tocopherol was not able to effectively eliminate the ROS produced inside cells. This counter effect was not observed in cells cultured in a traditional chamber slide, where no shear stress was present. This result suggests that the current microfluidic chip provides an in vitro platform best mimicking the physiological condition where cells are under circulating conditions. V C 2013 AIP Publishing LLC. [http://dx

show abstract

Are reactive oxygen species involved in Alzheimer's disease?

Cited by 333 publications

References 173 publications

Biochemistry and pathology of radical-mediated protein oxidation

Biochemistry and pathology of radical-mediated protein oxidation

The Mechanism of Mitochondrial Superoxide Production by the Cytochrome bc1 Complex

Effects of shear stresses and antioxidant concentrations on the production of reactive oxygen species in lung cancer cells

Contact Info

Product

Resources

About