Dilated cardiomyopathy and neonatal lethality in mutant mice lacking manganese superoxide dismutase

Li, Yibing; Huang, Ting‐Ting; Carlson, Elaine J.; Melov, Simon; Ursell, Philip C.; Olson, Jean L.; Noble, Linda; Yoshimura, Midori P.; Berger, Christoph; Chan, Pak H.; Wallace, Douglas C.; Epstein, Charles J.

doi:10.1038/ng1295-376

Cited by 1,601 publications

(1,110 citation statements)

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“…It has in fact been reported that Complex I generated superoxide is released exclusively into the matrix, together with 50% of the superoxide produced by Complex III (Muller et al, 2004). On the other hand, the key role of the mitochondrial SOD is illustrated by the lethal phenotype of mice lacking the matrix superoxide dismutase (Sod2) gene (Li et al, 1995). Finally, as described for osteogenic differentiation of human mesenchymal stem cells (Chen et al, 2008), our observations suggest that during DC differentiation a coordinated regulation between mitochondrial biogenesis and anti-oxidant defence systems needs to be orchestrated in order to let ROS production trigger differentiation but, at the same time, prevent accumulation of ROS when aerobic mitochondrial metabolism becomes dominant.…”

Section: Resultsmentioning

confidence: 99%

An active mitochondrial biogenesis occurs during dendritic cell differentiation

Zaccagnino

Saltarella

Maiorano

et al. 2012

The International Journal of Biochemistry & Cell Biology

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This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with colleagues.Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited. b s t r a c tDendritic cells (DC) are sentinels of the immune system deriving from circulating monocyte precursors recruited to sites of inflammation. In a previous report (Del Prete et al., 2008) we showed that, after differentiation, DC exhibited increased number of condensed mitochondria and dynamic changes in their energy metabolism. A study is presented here showing that the DC differentiation process is characterized by increased expression level and activity of mitochondrial respiratory complexes, as well as by an increased mitochondrial DNA (mtDNA) copy number. Moreover, DC are equipped with more efficient antioxidant protection systems, over expressed most likely to detoxify increased ROS production, as a consequence of the much higher mitochondrial activity. Kinetic analysis of the three main mitochondrial biogenesis-associated genes revealed that the peak in PPAR␥ coactivator-1alpha (PGC-1␣) gene expression was suddenly reached few hours after the onset of the differentiation. While PGC-1␣ expression rapidly declines, the mitochondrial transcription factor A (TFAM) and nuclear respiratory factor-1 (NRF-1) expression gradually increased. These findings demonstrate that an active mitochondrial biogenesis occurs during DC differentiation and further suggest that an early input by the master regulator of mitochondrial biogenesis PGC-1␣ is needed to trigger the subsequent activation of the downstream transcription factors, NRF-1 and TFAM in this process.

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Section: Resultsmentioning

confidence: 99%

An active mitochondrial biogenesis occurs during dendritic cell differentiation

Zaccagnino

Saltarella

Maiorano

et al. 2012

The International Journal of Biochemistry & Cell Biology

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“…The impact of altered redox homeostasis in loss of neuromuscular integrity and function with ageing has been investigated in several murine models, which have undergone genetic modifications of redox signalling/homeostasis components 19, 23, 25, 29, 30, 31, 32, 33, 34, 240, 241, 242. Transgenic murine models have provided insight into the importance of RONS regulatory systems in lifespan and neuromuscular ageing, and it has been reported that SOD2 −/− ,243 GRX3 −/− ,244 GPX4 −/− ,245 TRX1 −/− ,246 TRX2 −/− ,247 TR1 −/− 248 and TR2 −/− 249 murine models are embryonically lethal. Although the embryonic lethal phenotypes observed in these specific knockout models do not facilitate our understanding on whether defects in redox signalling affect age‐dependent deficits in neuromuscular integrity and function, these findings, however, highlight the fundamental importance of the redox systems mentioned in the preceding text during embryonic development.…”

Section: Non‐enzymatic Key Antioxidants That Contribute To the Maintementioning

confidence: 99%

Redox homeostasis and age‐related deficits in neuromuscular integrity and function

Sakellariou

Lightfoot

Earl

et al. 2017

J cachexia sarcopenia muscle

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Skeletal muscle is a major site of metabolic activity and is the most abundant tissue in the human body. Age‐related muscle atrophy (sarcopenia) and weakness, characterized by progressive loss of lean muscle mass and function, is a major contributor to morbidity and has a profound effect on the quality of life of older people. With a continuously growing older population (estimated 2 billion of people aged >60 by 2050), demand for medical and social care due to functional deficits, associated with neuromuscular ageing, will inevitably increase. Despite the importance of this ‘epidemic’ problem, the primary biochemical and molecular mechanisms underlying age‐related deficits in neuromuscular integrity and function have not been fully determined. Skeletal muscle generates reactive oxygen and nitrogen species (RONS) from a variety of subcellular sources, and age‐associated oxidative damage has been suggested to be a major factor contributing to the initiation and progression of muscle atrophy inherent with ageing. RONS can modulate a variety of intracellular signal transduction processes, and disruption of these events over time due to altered redox control has been proposed as an underlying mechanism of ageing. The role of oxidants in ageing has been extensively examined in different model organisms that have undergone genetic manipulations with inconsistent findings. Transgenic and knockout rodent studies have provided insight into the function of RONS regulatory systems in neuromuscular ageing. This review summarizes almost 30 years of research in the field of redox homeostasis and muscle ageing, providing a detailed discussion of the experimental approaches that have been undertaken in murine models to examine the role of redox regulation in age‐related muscle atrophy and weakness.

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“…The fast reaction of NO with , whereas the SOD2-repleted bacteria had only levels of ~10 -10 M. The critical role of SOD enzymes was revealed by Mn-SOD knockout mice, since they died within the first 10 days with a dilated cardiomyopathy and different metabolic abnormalties (Li et al, 1995). Cu/Zn deficient mice are viable, but highly sensitive to oxidative stress (Reaume et al, 1996).…”

Section: Superoxidementioning

confidence: 99%