The possible role of cytochrome c oxidase in stress-induced apoptosis and degenerative diseases

Kadenbach, Bernhard; Arnold, Susanne; Lee, Icksoo; Hüttemann, Maik

doi:10.1016/j.bbabio.2003.06.005

Cited by 204 publications

(160 citation statements)

References 91 publications

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“…It has been proposed that an increase in mitochondrial Ca 2ϩ concentration results in the activation of Ca 2ϩ -sensitive phosphatases, leading to the dephosphorylation of COX subunits. This leads to an increase in COX proton pumping and ⌬⌿ m (18). This would then result in elevated ROS production and could provide a fundamental explanation for the concurrent elevations in [Ca 2ϩ ] c , ROS, and ⌬⌿ m in patient cells compared with control cells.…”

Section: Discussionmentioning

confidence: 99%

Effect of thyroid hormone on mitochondrial properties and oxidative stress in cells from patients with mtDNA defects

Menzies

Robinson²,

Hood³

2009

American Journal of Physiology-Cell Physiology

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Section: Discussionmentioning

confidence: 99%

Effect of thyroid hormone on mitochondrial properties and oxidative stress in cells from patients with mtDNA defects

Menzies

Robinson²,

Hood³

2009

American Journal of Physiology-Cell Physiology

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“…This latter association has been widely referred to (36,37), but strict scientific evidence for it is lacking. However, this unexpected reduction in oxidative damage is in agreement with previous findings that a mutation in the mitochondrial leucyl-tRNA synthetase gene (38), a point mutation in a gene that encodes the iron sulfur protein of complex III (39), and caloric restriction (40), all of which reduce oxygen consumption and extend lifespan, appear to reduce oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

Cytochrome c oxidase deficiency in neurons decreases both oxidative stress and amyloid formation in a mouse model of Alzheimer's disease

Fukui¹,

Díaz²,

Garcia³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

164

133

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Defects in the mitochondrial cytochrome c oxidase (COX) have been associated with Alzheimer's Disease, in which the agedependent accumulation of ␤-amyloid plays an important role in synaptic dysfunction and neurodegeneration. To test the possibility that age-dependent decline in the mitochondrial respiratory function, especially COX activity, may participate in the formation and accumulation of ␤-amyloid, we generated mice expressing mutant amyloid precursor protein and mutant presenilin 1 in a neuron-specific COX-deficient background. A neuron-specific COXdeficient mouse was generated by the Cre-loxP system, in which the COX10 gene was deleted by a CamKII␣ promoter-driven Crerecombinase. COX10 is a farnesyltransferase involved in the biosynthesis of heme a, required for COX assembly and function. These KO mice showed an age-dependent COX deficiency in the cerebral cortex and hippocampus. Surprisingly, COX10 KO mice exhibited significantly fewer amyloid plaques in their brains compared with the COX-competent transgenic mice. This reduction in amyloid plaques in the KO mouse was accompanied by a reduction in A␤42 level, ␤-secretase activity, and oxidative damage. Likewise, production of reactive oxygen species from cells with partial COX activity was not elevated. Collectively, our results suggest that, contrary to previous models, a defect in neuronal COX does not increase oxidative damage nor predispose for the formation of amyloidgenic amyloid precursor protein fragments. mitochondria ͉ oxidative phosphorylation ͉ neurodegeneration A lzheimer's disease (AD) is the most prevalent age-related neurodegenerative disease, characterized by progressive brain atrophy/neuronal death that results in cognitive and memory impairment. Starting from the identification of genes responsible for familial AD, which is now known to constitute only Ͻ5% of total AD incidence, an ''amyloid hypothesis'' has been built up during the past few decades, and an enormous effort has been devoted to understand the toxic mechanism of ␤-amyloid (A␤), which forms extracellular amyloid plaques and is generated by a successive proteolytic cleavage of amyloid precursor protein (APP) by ␤-secretase and a ␥-secretase complex containing presenilins (1). Although it is not clear to what extent different A␤ species (soluble oligomers, insoluble aggregates, extracellular species, or intracellular species) contribute to neurodegeneration in vivo, recent studies demonstrated the toxicity of diverse A␤ species in vitro, in situ, and in vivo, confirming the importance of age-dependent A␤ accumulation in AD pathogenesis (2-5).Recently, age-dependent accumulation of mutations in mitochondrial DNA (mtDNA) and resulting increase in oxidative stress and impairment in mitochondrial respiratory chain, especially complex IV or cytochrome c oxidase (COX), gained attention as potential factors that could participate in the onset of sporadic AD (6). A number of studies reported a reduction in COX activity and an increase in oxidative stress in brain tissues and plate...

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“…34 The release of cytochrome c from mitochondria to the cytoplasm can trigger apoptosis in osteoblasts. 35 Oxidative stress increased the cellular levels of cytochrome c protein.…”

Section: Discussionmentioning

confidence: 99%

Nitric oxide protects osteoblasts from oxidative stress‐induced apoptotic insults via a mitochondria‐dependent mechanism

Chang

Liao

Lin

et al. 2006

Journal Orthopaedic Research

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Nitric oxide (NO) contributes to the regulation of osteoblast activities. In this study, we evaluated the protective effects of NO pretreatment on oxidative stress-induced osteoblast apoptosis and its possible mechanism using neonatal rat calvarial osteoblasts as the experimental model. Exposure of osteoblasts to sodium nitroprusside (SNP) at a low concentration of 0.3 mM significantly increased cellular NO levels without affecting cell viability. However, when the concentration reached a high concentration of 2 mM, SNP increased the levels of intracellular reactive oxygen species and induced osteoblast injuries. Thus, administration of 0.3 and 2 mM SNP in osteoblasts were respectively used as sources of NO and oxidative stress. Pretreatment with NO for 24 h significantly ameliorated the oxidative stress-caused morphological alterations and decreases in alkaline phosphatase activity, and reduced cell death. Oxidative stress induced osteoblast death via an apoptotic mechanism, but NO pretreatment protected osteoblasts against the toxic effects. The mitochondrial membrane potential was significantly reduced following exposure to the oxidative stress. However, pretreatment with NO significantly lowered the suppressive effects. Oxidative stress increased cellular Bax protein production and cytochrome c release from mitochondria. Pretreatment with NO significantly decreased oxidative stress-caused augmentation of Bax and cytochrome c protein levels. In parallel with cytochrome c release, oxidative stress induced caspase-3 activation and DNA fragmentation. Pretreatment with NO significantly reduced the oxidative stress-enhanced caspase-3 activation and DNA damage. Results of this study show that NO pretreatment can protect osteoblasts from oxidative stress-induced apoptotic insults. The protective action involves a mitochondria-dependent mechanism. ß

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The possible role of cytochrome c oxidase in stress-induced apoptosis and degenerative diseases

Cited by 204 publications

References 91 publications

Effect of thyroid hormone on mitochondrial properties and oxidative stress in cells from patients with mtDNA defects

Effect of thyroid hormone on mitochondrial properties and oxidative stress in cells from patients with mtDNA defects

Cytochrome c oxidase deficiency in neurons decreases both oxidative stress and amyloid formation in a mouse model of Alzheimer's disease

Nitric oxide protects osteoblasts from oxidative stress‐induced apoptotic insults via a mitochondria‐dependent mechanism

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