Impairment of Brain Mitochondrial Oxidative Phosphorylation Accompanying Vitamin E Oxidation Induced by Iron or Reactive Nitrogen Species: A Selective Review

Vatassery, Govind T.

doi:10.1007/s11064-004-6870-4

Cited by 15 publications

(3 citation statements)

References 56 publications

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“…The depressed expression of the Class 1 and 4 complexes of the electron transport respiratory chain were clearly evident as well as genes that regulate the coupling of oxidative phosphorylation to ATP synthesis. Peroxynitrite, iron as well as reactive oxygen and nitrogen species are all highly expressed in aging white matter and have been demonstrated to impair mitochondrial respiration (Lu et al, 2004;Mecocci et al, 1993;Vatassery, 2004).…”

Section: Discussion Functional Gene Groups Identified To Be Involved mentioning

confidence: 99%

Gene profile analysis implicates Klotho as an important contributor to aging changes in brain white matter of the rhesus monkey

Duce

Podvin

Hollander

et al. 2007

Glia

116

100

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Conventional studies of brain changes in normal aging have concentrated on gray matter as the locus for cognitive dysfunction. However, there is accumulating evidence from studies of normal aging in the rhesus monkey that changes in white matter may be a more critical factor in cognitive decline. Such changes include ultrastructural and biochemical evidence of myelin breakdown with age, as well as more recent magnetic resonance imaging of global loss of forebrain white matter volume and magnetic resonance diffusion tension imaging evidence of increased diffusivity in white matter. Moreover, many of these white matter changes correlate with age-related cognitive dysfunction. Based on these diverse white matter findings, the present work utilized high-density oligonucleotide microarrays to assess gene profile changes associated with age in the white matter of the corpus callosum. This approach identified several classes of genes that were differentially expressed in aging. Broadly characterized, these genes were predominantly related to an increase in stress factors and a decrease in cell function. The cell function changes included increased cell cycle inhibition and proteolysis, as well as decreased mitochondrial function, signal transduction, and protein translation. While most of these categories have previously been reported in functional brain aging, this is the first time they have been associated directly with white matter. Microarray analysis has also enabled the identification of neuroprotective response pathways activated by age in white matter, as well as several genes implicated in lifespan. Of particular interest was the identification of Klotho, a multifunctional protein that regulates phosphate and calcium metabolism, as well as insulin resistance, and is known to defend against oxidative stress and apoptosis. Combining the findings from the microarray study enabled us to formulate a model of white matter aging where specific genes are suggested as primary factors in disrupting white matter function. In conclusion, the overall changes described in this study could provide an explanation for aging changes in white matter that might be initiated or enhanced by an altered expression of life span associated genes such as Klotho.

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Section: Discussion Functional Gene Groups Identified To Be Involved mentioning

confidence: 99%

Gene profile analysis implicates Klotho as an important contributor to aging changes in brain white matter of the rhesus monkey

Duce

Podvin

Hollander

et al. 2007

Glia

116

100

View full text Add to dashboard Cite

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“…Either low state 3 or high state 4 respiration is observed in iron overload together with the low RCR. State 4 respiration, in particular, is a common consequence of uncoupling (6). Uncoupling often occurs in the presence of iron and consumes ATP (7).…”

Section: Heart Weight and Mitochondrial Atp Content Ros And Rcr Of mentioning

confidence: 99%

Increased expression of the F₁F_o ATP synthase in response to iron in heart mitochondria

Kim

Cheon

et al. 2008

BMB Reports

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“…RCR was low during this period, which was least at 48 h (64% of 0 h) with slight recovery at 72 h (68% of 0 h). In the presence of iron as an uncoupler (Vatassery 2004), normal levels of state IV may not be attained due to low levels of ATP. The resulting high levels of ADP yielded low RCR.…”

Section: Changes In Calcium Content Nad(p)h Rcr and Membrane Potenmentioning

confidence: 99%

Temporal changes in mitochondrial activities of rat heart after a single injection of iron, including increased complex II activity

Kim

Song

2010

Animal Cells and Systems

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Male rats were given a single injection of iron, and temporal changes in iron content and iron-induced effects were examined in heart cellular fractions. Over a period of 72 h, the contents of total and labile iron, reactive oxygen species, and NO in tissue homogenate, nuclear debris, and postmitochondrial fractions were mostly constant, but in mitochondria they continuously increased. An abrupt decrease in membrane potential and NAD(P)H at 12 h was also found in mitochondria. The respiratory control ratio was reduced slowly with a slight recovery at 72 h, suggesting uncoupling by iron. While the ATP content of tissue homogenate decreased steadily until 72 h, it showed a prominent increase in mitochondria at 12 h. Total iron and calcium concentration also progressively increased in mitochondria over 72 h. Enzyme activity of the oxidative phosphorylation system was significantly altered by iron injection: activities of complexes I, III, and IV were reduced considerably, but complex II activity and the ATPase activity of complex V were enhanced. A reversal of activity in complexes I and II at 12 h suggested reverse electron transfer due to iron overload. These results support the argument that mitochondrial activities including oxidative phosphorylation are modulated by excessive iron.

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Impairment of Brain Mitochondrial Oxidative Phosphorylation Accompanying Vitamin E Oxidation Induced by Iron or Reactive Nitrogen Species: A Selective Review

Cited by 15 publications

References 56 publications

Gene profile analysis implicates Klotho as an important contributor to aging changes in brain white matter of the rhesus monkey

Gene profile analysis implicates Klotho as an important contributor to aging changes in brain white matter of the rhesus monkey

Increased expression of the F₁F_o ATP synthase in response to iron in heart mitochondria

Temporal changes in mitochondrial activities of rat heart after a single injection of iron, including increased complex II activity

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Impairment of Brain Mitochondrial Oxidative Phosphorylation Accompanying Vitamin E Oxidation Induced by Iron or Reactive Nitrogen Species: A Selective Review

Cited by 15 publications

References 56 publications

Gene profile analysis implicates Klotho as an important contributor to aging changes in brain white matter of the rhesus monkey

Gene profile analysis implicates Klotho as an important contributor to aging changes in brain white matter of the rhesus monkey

Increased expression of the F1Fo ATP synthase in response to iron in heart mitochondria

Temporal changes in mitochondrial activities of rat heart after a single injection of iron, including increased complex II activity

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Increased expression of the F₁F_o ATP synthase in response to iron in heart mitochondria