cytochrome-c-t and Muscular-Diseases

Topics: Cytochrome-c Oxidase Deficiency; Cytochromes c; Female; Heart; Humans; Infant, Newborn; Mitochondria; Muscular Diseases; Pregnancy

Side effects and toxicity have posed a threat to the positive contribution of Antiretroviral Therapy (ART) in the management of human immunodeficiency virus (HIV) infection and Acquired Immune Deficiency Syndrome (AIDS). Symptoms of mitochondrial toxicity including myopathy, pancreatitis, hyperlipidaemia and lactic acidosis are found among HIVinfected patients on ART. To date, there is not a reliable biomarker for monitoring ART-related mitochondrial toxicity. Plasma level of Cytochrome c (Cyt-c) has been proposed as a potential biomarker for ART-related toxicity due to its strong association with apoptosis.. The present study assessed toxicity and level of plasma Cyt-c among HIV-infected patients receiving ART in Ghana.. A total of eighty (80) HIV patients were recruited into the study. Demographic data were obtained from personal interview and medical records. Plasma samples were screened for toxicity from sixty (60) participants due to limited resources, and plasma Cyt-c levels were determined using ELISA. Data were analyzed using Stata version 13.. Out of the 60 participants, 11 (18.3%) were found with symptoms of myopathy, 12 (20%) with pancreatitis, 21 (35%) with hyperlipidaemia and 36 (60%) with at least one of the symptoms. The concentration of plasma Cyt-c was higher (0.122 ng/ml) in patients with toxicity than in those without toxicity (0.05 ng/ml), though the difference was not statistically significant (p = 0.148). There was a weak correlation between plasma Cyt-c level and duration of ART (Spearman rho = 0.02, p = 0.89).. This study, therefore, demonstrated a high prevalence of ART-related toxicity and high levels of Cyt-c in HIV-infected patients in support of the argument that plasma Cyt-c levels are potential biomarkers for determining ART-related toxicity in HIV patients.

Topics: Adult; Antiretroviral Therapy, Highly Active; Cross-Sectional Studies; Cytochromes c; Drug-Related Side Effects and Adverse Reactions; Female; Ghana; HIV Infections; Humans; Hyperlipidemias; Male; Middle Aged; Muscular Diseases; Pancreatitis; Young Adult

Muscle diseases display mitochondrial dysfunction and oxidative damage. Our previous study in a cardiotoxin model of myodegeneration correlated muscle damage with mitochondrial dysfunction, which in turn entailed altered mitochondrial proteome and oxidative damage of mitochondrial proteins. Proteomic identification of oxidized proteins in muscle biopsies from muscular dystrophy patients and cardiotoxin model revealed specific mitochondrial proteins to be targeted for oxidation. These included respiratory complexes which displayed oxidative modification of Trp residues in different subunits. Among these, Ubiquinol-Cytochrome C Reductase Core protein 1 (UQCRC1), a subunit of Ubiquinol-Cytochrome C Reductase Complex or Cytochrome b-c1 Complex or Respiratory Complex III displayed oxidation of Trp395, which could be correlated with the lowered activity of Complex III. We hypothesized that Trp395 oxidation might contribute to altered local conformation and overall structure of Complex III, thereby potentially leading to altered protein activity. To address this, we performed molecular dynamics simulation of Complex III (oxidized at Trp395 of UQCRC1 vs. non-oxidized control). Molecular dynamic simulation analyses revealed local structural changes in the Trp395 site. Intriguingly, oxidized Trp395 contributed to decreased plasticity of Complex III due to significant cross-talk among the subunits in the matrix-facing region and subunits in the intermembrane space, thereby leading to impaired electron flow from cytochrome C.

Topics: Animals; Cytochromes c; Electron Transport Complex III; Mice; Molecular Dynamics Simulation; Muscular Diseases; Oxidation-Reduction; Tryptophan

An 8-year-old male Japanese Shiba exhibited muscle wasting and a stiff gait. A low-amplitude myotonic discharge was recorded by needle electromyography (EMG). A histopathological examination on a tru-cut biopsy sample from the muscle revealed myofiber size variations. Internal nuclei and cytoplasmic vacuoles were observed in many fibers. A type 1 fiber predominance and many hybrid type fibers were observed immunohistochemically. On the basis of these EMG and histopathological findings, myotonic dystrophy (DM) was suspected as tentative diagnosis. The cytoplasm around the vacuoles was immunopositive for cytochrome c, tom 20, and SOD-1, suggesting that these vacuoles might occur within mitochondria. Collectively, these results indicate that a mitochondrial abnormality partly play the role on the pathogenesis of present case.

Topics: Animals; Biopsy, Needle; Cytochromes c; Dog Diseases; Dogs; Electromyography; Male; Mitochondrial Diseases; Muscle, Skeletal; Muscular Diseases; Myotonic Dystrophy; Superoxide Dismutase-1

In addition to their lipid-lowering effect, statins have pleiotropic effects that may extend their use to the treatment and prevention of various other diseases such as cancer, osteoporosis, multiple sclerosis, rheumatoid arthritis, type 2 diabetes, and Alzheimer's disease. Consequently, the number of patients taking statins is expected to increase. A side effect of statins, statin-induced myopathy, which may result from reduced muscular coenzyme Q10 levels, limits their use. The current study investigates if supplementing with CoQ10 could ameliorate statin induced myopathy.. Forty adult male albino rats were randomized into 4 groups, with 10 rats per group. The following was administered to the rats using oral gavage for 4 weeks: Group 1: 2 ml of 0.5% carboxymethyl cellulose once daily. Group 2: 100 mg/kg/ day coenzyme Q10 dissolved in 2 ml of cotton seed oil. Group 3: 10 mg/kg once daily atorvastatin dissolved in 0.5% carboxymethyl cellulose. Group 4: concomitantly received CoQ10 and atorvastatin similar to groups 2 and 3 respectively. Plasma creatine kinase levels were measured by using spectrophotometer. The right extensor digitorum longus muscle sections were stained for histological (Haematoxylin & Eosin, Masson trichrome and Phosphotungstic acid haematoxylin) and immunohistochemical (cytochrome C and Bax) examinations. Quantitative measures of cytochrome C and Bax were carried out using image analyzer.. Atorvastatin induced increased total creatine kinase, skeletal muscle variations in the sizes and shapes, necrosis, disorganization, nuclear pyknosis, karyorrhexis, karyolysis, dismantled plasma membrane, excess collagen fibers and lipid deposition in addition to loss of cross striation. Atorvastatin increased the intensity of the immune-positive reactions of cytochrome C and Bax. These changes were ameliorated by concomitantly giving coenzyme Q10.. CoQ10 may ameliorate atorvastatin induced skeletal muscle injury.

Topics: Animals; Atorvastatin; bcl-2-Associated X Protein; Creatine Kinase; Cytochromes c; Heptanoic Acids; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Immunohistochemistry; Male; Muscle, Skeletal; Muscular Diseases; Protective Agents; Pyrroles; Rats; Ubiquinone

Barth syndrome (BTHS) is an X-linked recessive disorder that is biochemically characterized by low cellular levels of the mitochondrial phospholipid cardiolipin (CL). Previously, we discovered that the yeast disruptant of the TAZ ortholog in Saccharomyces cerevisiae not only displays CL deficiency but also accumulates monolysocardiolipins (MLCLs), which are intermediates in CL remodeling. Therefore, we set out to investigate whether MLCL accumulation also occurs in BTHS. Indeed, we observed MLCL accumulation in heart, muscle, lymphocytes, and cultured lymphoblasts of BTHS patients; however, only very low levels of these lysophospholipids were found in platelets and fibroblasts of these patients. Although the fatty acid composition of the MLCLs was different depending on the tissue source, it did parallel the fatty acid composition of the (remaining) CLs. The possible implications of these findings for the two reported CL remodeling mechanisms, transacylation and deacylation/reacylation, are discussed. Because MLCLs have been proposed to be involved in the initiation of apoptosome-mediated cell death by the sequestration of the proapoptotic protein (t)BH3-interacting domain death agonist (Bid) to the mitochondrial membrane, we used control and BTHS lymphoblasts to investigate whether the accumulation of MLCLs results in higher levels of apoptosis. We found no differences in susceptibility to death receptor-mediated apoptosis or in cellular distribution of Bid, cytochrome c, and other parameters, implying that MLCL accumulation does not lead to enhanced apoptosis in cultured BTHS lymphoblasts.

Topics: Acylation; Apoptosis; BH3 Interacting Domain Death Agonist Protein; Cardiolipins; Cardiomyopathies; Carrier Proteins; Cell Death; Chromatography, High Pressure Liquid; Chromosomes, Human, X; Cytochromes c; fas Receptor; Genes, Recessive; Genetic Linkage; Growth Disorders; Humans; Immunoblotting; Jurkat Cells; Lipid Metabolism; Lymphocytes; Lysophospholipids; Mass Spectrometry; Mitochondria; Muscles; Muscular Diseases; Myocardium; Phospholipids; Poly(ADP-ribose) Polymerases; Protein Structure, Tertiary; Subcellular Fractions; Syndrome

Topics: Cytochromes; Cytochromes c; Humans; Muscles; Muscular Diseases; Muscular Dystrophies

Topics: Cytochromes; Cytochromes c; Humans; Muscular Diseases; Muscular Dystrophies