Mitochondrial Alterations and Oxidative Stress in an Acute Transient Mouse Model of Muscle Degeneration

Ramadasan-Nair, Renjini; Gayathri, Narayanappa; Mishra, Sumeet; Sunitha, B.; Mythri, Rajeswara Babu; Nalini, Atchayaram; Subbannayya, Yashwanth; Harsha, H. C.; Kolthur‐Seetharam, Ullas; Bharath, M. M. Srinivas

doi:10.1074/jbc.m113.493270

Cited by 63 publications

(82 citation statements)

References 91 publications

(57 reference statements)

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“…Consistent with our observations (spots 25 and 26 in Fig. 3), a recent study on tibialis anterior muscle of DMD patients [16] showed aconitate hydratase to be overcarbonylated. Also in agreement with our study, mitochondrial proteins appeared to be preferential targets of carbonylation in dystrophic muscle.…”

Section: Discussionsupporting

confidence: 92%

“…One of the most common types of oxidative modification is protein carbonylation, the introduction of carbonyl groups (C¼O) in a protein [12]. We chose protein carbonylation as a marker of oxidative stress, because it is a reliable indicator of oxidative damages [13], suitable for proteomic analysis [14] and commonly used on mdx muscle [15,16]. Studies reported an abnormal oxidative stress in skeletal muscle of DMD patients and mdx mice [17,18].…”

Section: Introductionmentioning

confidence: 99%

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Low intensity training of mdx mice reduces carbonylation and increases expression levels of proteins involved in energy metabolism and muscle contraction

Hyzewicz

Tanihata

Kuraoka

et al. 2015

Free Radical Biology and Medicine

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High intensity training induces muscle damage in dystrophin-deficient mdx mice, an animal model for Duchenne muscular dystrophy. However, low intensity training (LIT) rescues the mdx phenotype and even reduces the level of protein carbonylation, a marker of oxidative damage. Until now, beneficial effects of LIT were mainly assessed at the physiological level. We investigated the effects of LIT at the molecular level on 8-week-old wild-type and mdx muscle using 2D Western blot and protein-protein interaction analysis. We found that the fast isoforms of troponin T and myosin binding protein C as well as glycogen phosphorylase were overcarbonylated and downregulated in mdx muscle. Some of the mitochondrial enzymes of the citric acid cycle were overcarbonylated, whereas some proteins of the respiratory chain were downregulated. Of functional importance, ATP synthase was only partially assembled, as revealed by Blue Native PAGE analysis. LIT decreased the carbonylation level and increased the expression of fast isoforms of troponin T and of myosin binding protein C, and glycogen phosphorylase. In addition, it increased the expression of aconitate hydratase and NADH dehydrogenase, and fully restored the ATP synthase complex. Our study demonstrates that the benefits of LIT are associated with lowered oxidative damage as revealed by carbonylation and higher expression of proteins involved in energy metabolism and muscle contraction. Potentially, these results will help to design therapies for DMD based on exercise mimicking drugs.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Low intensity training of mdx mice reduces carbonylation and increases expression levels of proteins involved in energy metabolism and muscle contraction

Hyzewicz

Tanihata

Kuraoka

et al. 2015

Free Radical Biology and Medicine

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“…GSH/GSSG ratio was determined by the o‐pthalaldehyde method (Hissin and Hilf ; Ramadasan‐Nair et al . ). Superoxide dismutase (EC 1.15.1.1) (SOD) activity was determined as described (Bagnyukova et al .…”

Section: Methodsmentioning

confidence: 97%

Characterization of traumatic brain injury in human brains reveals distinct cellular and molecular changes in contusion and pericontusion

Harish

Mahadevan

Pruthi

et al. 2015

Journal of Neurochemistry

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Traumatic brain injury (TBI) contributes to fatalities and neurological disabilities worldwide. While primary injury causes immediate damage, secondary events contribute to long-term neurological defects. Contusions (Ct) are primary injuries correlated with poor clinical prognosis, and can expand leading to delayed neurological deterioration. Pericontusion (PC) (penumbra), the region surrounding Ct, can also expand with edema, increased intracranial pressure, ischemia, and poor clinical outcome. Analysis of Ct and PC can therefore assist in understanding the pathobiology of TBI and its management. This study on human TBI brains noted extensive neuronal, astroglial and inflammatory changes, alterations in mitochondrial, synaptic and oxidative markers, and associated proteomic profile, with distinct differences in Ct and PC.While Ct displayed petechial hemorrhages, thrombosis, inflammation, neuronal pyknosis, and astrogliosis, PC revealed edema, vacuolation of neuropil, axonal loss, and dystrophic changes. Proteomic analysis demonstrated altered immune response, synaptic, and mitochondrial dysfunction, among others, in Ct, while PC displayed altered regulation of neurogenesis and cytoskeletal architecture, among others. TBI brains displayed oxidative damage, glutathione depletion, mitochondrial dysfunction, and loss of synaptic proteins, with these changes being more profound in Ct. We suggest that analysis of markers specific to Ct and PC may be valuable in the evaluation of TBI pathobiology and therapeutics.

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“…The mitochondrion is an essential organelle acting as the hub of energy production, central metabolism, and other activities, such as calcium signaling and regulation of apoptosis. Accumulation of mitochondrial damage leads to loss of function of the organelle and is implicated in aging and related diseases such as neurodegeneration and muscle myopathies (McFaline‐Figueroa et al ., ; Lopez‐Otin et al ., ; Ramadasan‐Nair et al ., ; Stauch et al ., ). Dysfunctional mitochondria are characterized by lower ATP production, decreased membrane potential (∆ψ), loss of or damage to mitochondrial DNA (mtDNA), increased ROS production, and more oxidizing redox states (Green et al ., ; McFaline‐Figueroa et al ., ; Park & Larsson, ; Hughes & Gottschling, ).…”

Section: Asymmetric Inheritance Of Aging Determinants In Cell Divisiomentioning

confidence: 99%

Role of asymmetric cell division in lifespan control inSaccharomyces cerevisiae

et al. 2014

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Aging determinants are asymmetrically distributed during cell division in S. cerevisiae, which leads to production of an immaculate, age-free daughter cell. During this process, damaged components are sequestered and retained in the mother cell, and higher functioning organelles and rejuvenating factors are transported to and/or enriched in the bud. Here, we will describe the key quality control mechanisms in budding yeast that contribute to asymmetric cell division of aging determinants including mitochondria, endoplasmic reticulum (ER), vacuoles, extrachromosomal rDNA circles (ERCs), and protein aggregates.

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Mitochondrial Alterations and Oxidative Stress in an Acute Transient Mouse Model of Muscle Degeneration

Cited by 63 publications

References 91 publications

Low intensity training of mdx mice reduces carbonylation and increases expression levels of proteins involved in energy metabolism and muscle contraction

Low intensity training of mdx mice reduces carbonylation and increases expression levels of proteins involved in energy metabolism and muscle contraction

Characterization of traumatic brain injury in human brains reveals distinct cellular and molecular changes in contusion and pericontusion

Role of asymmetric cell division in lifespan control inSaccharomyces cerevisiae

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