Hydroperoxide metabolism in mammalian organs.

Chance, B; Sies, Helmut; Boveris, Alberto

doi:10.1152/physrev.1979.59.3.527

Cited by 5,307 publications

(2,814 citation statements)

References 56 publications

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“…Both NADH-ubiquinone reductase and ubiquinone-cytochrome c reductase generate O~ and H202 (6). Because the transition from a twoelectron (NADH and FADH2) to a one-electron (ubiquinone) transfer involves the formation of semiubiquinone (QH~ this segment of the ETC becomes a primary site for O~ production (6).…”

Section: Mitochondrial Theorymentioning

confidence: 99%

“…A metal-catalyzed Fenton reaction or HaberWeiss reaction between O~ and H202 may give rise to "OH (1). Liver mitochondria is estimated to produce 24 nmol O~ rain per g of tissue; with an active conversion to H202 by SOD, a steady-state O~ concentration of 8x10 .8 M can be derived (6). Heart mitochondria generate 0.3-0.6 nmol/min per mg protein representing 2% of the tissue's total oxygen consumption.…”

Section: Mitochondrial Theorymentioning

confidence: 99%

“…Thus, higher organisms have developed effective antioxidant systems during the course of evolution (1,6). In general, the cell has adequate antioxidant reserves to cope with the production of ROS under physiological conditions such that these toxic compounds do not accumulate.…”

Section: Introductionmentioning

confidence: 99%

“…The system consists of antioxidant vitamins (water-soluble ascorbic acid and fat-soluble a-tocopherol and b-carotene), thiol-containing, low-molecular weight compounds, mainly glutathione (GSH), and antioxidant enzymes, such as superoxide dismutase (SOD), GSH peroxidase (GPX), and catalase (CAT). Each of these antioxidants plays a unique role in the cell and complements one another geographically and functionally (6). Furthermore, there is evidence that certain antioxidants, such as GSH, may be involved in interorgan transport (7).…”

Section: Introductionmentioning

confidence: 99%

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Exercise and oxidative stress: Sources of free radicals and their impact on antioxidant systems

Leichtweis

1997

AGE

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Strenuous exercise is characterized by increased oxygen consumption and the disturbance between intracellular pro-oxidant and antioxidant homeostasis. At lease three biochemical pathways (i.e., mitochondrial electron transport chain, xanthine oxidase, and polymorphoneutrophil) have been identified as potential sources of intracellular free radical generation during exercise. These deleterious reactive oxygen species pose a serious threat to the cellular antioxidant defense system, such as diminished reserves of antioxidant vitamins and glutathione. However, enzymatic and non-enzymatic antioxidants have demonstrated great versitility and adaptability in response to acute and chronic exercise. The delicate balance between pro-oxidants and antioxidants suggests that supplementation with antioxidants may be desirable for physically active individuals under certain physiological conditions by providing a larger protective margin.

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Section: Mitochondrial Theorymentioning

confidence: 99%

Section: Mitochondrial Theorymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Exercise and oxidative stress: Sources of free radicals and their impact on antioxidant systems

Leichtweis

1997

AGE

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“…The production of mdROS was modeled as a fraction, or shunt , of electrons from the electron transport chain into the matrix, as previously described 5, 47, 51, 52. Studies have shown that under physiological conditions, up to 2% of the electron flowing the respiratory chain are partially reduced to form the superoxide,53 thus the physiological value of shunt was set as 2%. Pathological shunt was set as 10% or 14% to induce sustained mitochondrial oscillations, which is consistent with our previous computational studies 5, 47, 52.…”

Section: Methodsmentioning

confidence: 99%

Mitochondrial‐Mediated Oxidative Ca ²⁺ /Calmodulin‐Dependent Kinase II Activation Induces Early Afterdepolarizations in Guinea Pig Cardiomyocytes: An In Silico Study

Yang

Erñst

Song

et al. 2018

JAHA

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BackgroundOxidative stress–mediated Ca2+/calmodulin‐dependent protein kinase II (CaMKII) phosphorylation of cardiac ion channels has emerged as a critical contributor to arrhythmogenesis in cardiac pathology. However, the link between mitochondrial‐derived reactive oxygen species (mdROS) and increased CaMKII activity in the context of cardiac arrhythmias has not been fully elucidated and is difficult to establish experimentally.Methods and ResultsWe hypothesize that pathological mdROS can cause erratic action potentials through the oxidation‐dependent CaMKII activation pathway. We further propose that CaMKII‐dependent phosphorylation of sarcolemmal slow Na+ channels alone is sufficient to elicit early afterdepolarizations. To test the hypotheses, we expanded our well‐established guinea pig cardiomyocyte excitation‐contraction coupling, mitochondrial energetics, and ROS‐induced‐ROS‐release model by incorporating oxidative CaMKII activation and CaMKII‐dependent Na+ channel phosphorylation in silico. Simulations show that mdROS mediated‐CaMKII activation elicits early afterdepolarizations by augmenting the late Na+ currents, which can be suppressed by blocking L‐type Ca2+ channels or Na+/Ca2+ exchangers. Interestingly, we found that oxidative CaMKII activation–induced early afterdepolarizations are sustained even after mdROS has returned to its physiological levels. Moreover, mitochondrial‐targeting antioxidant treatment can suppress the early afterdepolarizations, but only if given in an appropriate time window. Incorporating concurrent mdROS‐induced ryanodine receptors activation further exacerbates the proarrhythmogenic effect of oxidative CaMKII activation.ConclusionsWe conclude that oxidative CaMKII activation–dependent Na channel phosphorylation is a critical pathway in mitochondria‐mediated cardiac arrhythmogenesis.

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White Matter Structural Integrity in Healthy Aging Adults and Patients With Alzheimer Disease

Bartzokis¹,

Cummings

Sultzer³

et al. 2003

Arch Neurol

367

301

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The R(2) changes in white matter suggest that the healthy adult brain is in a constant state of change, roughly defined as periods of maturation continuing into middle age followed by progressive loss of myelin integrity. Clinically diagnosed AD is associated with more severe myelin breakdown. Noninvasive measures, such as the determination of the R(2), may have the potential to track prospectively the trajectory of deteriorating white matter integrity during normal aging and the development of AD and, thus, may be a useful marker for medication development aimed at the prevention of AD.

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Hydroperoxide metabolism in mammalian organs.

Cited by 5,307 publications

References 56 publications

Exercise and oxidative stress: Sources of free radicals and their impact on antioxidant systems

Exercise and oxidative stress: Sources of free radicals and their impact on antioxidant systems

Mitochondrial‐Mediated Oxidative Ca ²⁺ /Calmodulin‐Dependent Kinase II Activation Induces Early Afterdepolarizations in Guinea Pig Cardiomyocytes: An In Silico Study

White Matter Structural Integrity in Healthy Aging Adults and Patients With Alzheimer Disease

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Hydroperoxide metabolism in mammalian organs.

Cited by 5,307 publications

References 56 publications

Exercise and oxidative stress: Sources of free radicals and their impact on antioxidant systems

Exercise and oxidative stress: Sources of free radicals and their impact on antioxidant systems

Mitochondrial‐Mediated Oxidative Ca 2+ /Calmodulin‐Dependent Kinase II Activation Induces Early Afterdepolarizations in Guinea Pig Cardiomyocytes: An In Silico Study

White Matter Structural Integrity in Healthy Aging Adults and Patients With Alzheimer Disease

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Mitochondrial‐Mediated Oxidative Ca ²⁺ /Calmodulin‐Dependent Kinase II Activation Induces Early Afterdepolarizations in Guinea Pig Cardiomyocytes: An In Silico Study