Depletion of mitochondrial DNA in the skeletal muscle of two cirrhotic patients with severe asthenia

Pesce, Vito; Cormio, Antonella; Marangi, L.; Guglielmi, Francesco William; Lezza, Angela Maria Serena; Francavilla, A.; Cantatore, Palmiro; Gadaleta, Maria Nicola

doi:10.1016/s0378-1119(01)00815-0

Cited by 11 publications

(7 citation statements)

References 31 publications

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“…As expected, these clinico-pathological parameters reflected the damaged liver function and the destruction of hepatocellular carcinoma tissues. Our data were consistent with an earlier study showing that mtDNA content was correlated with cirrhosis [52], and that HCC patients with cirrhosis had elevated mtDNA content. Paradoxically, we have found that the moderate hepatitis group showed lower 5-mC content than the mild hepatitis group, while no differences were found between other groups.…”

Section: Discussionsupporting

confidence: 93%

Association of 5-Methylcytosine and 5-Hydroxymethylcytosine with Mitochondrial DNA Content and Clinical and Biochemical Parameters in Hepatocellular Carcinoma

Shen

Huang

et al. 2013

PLoS ONE

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Increasing epidemiological evidence has indicated that inherited variations of mitochondrial DNA (mtDNA) copy number affect the genetic susceptibility of many malignancies in a tumour-specific manner and that DNA methylation also plays an important role in controlling gene expression during the differentiation and development of hepatocellular carcinoma (HCC). Our previous study demonstrated that HCC tissues showed a lower 5-hydroxymethylcytosine (5-hmC) content when compared to tumour-adjacent tissues, but the relationship among 5-hmC, 5-methylcytosine (5-mC) and mtDNA content in HCC patients is still unknown. This study aimed to clarify the correlation among mtDNA content, 5-mC and 5-hmC by quantitative real-time PCR and liquid chromatography tandem mass spectrometry analysis. We demonstrated that 5-hmC correlated with tumour size [odds ratio (OR) 0.847, 95% confidence interval (CI) 0.746–0.962, P = 0.011], and HCC patients with a tumour size ≥5.0 cm showed a lower 5-hmC content and higher levels of fasting plasma aspartate aminotransferase, the ratio of alanine amiotransferase to aspartate aminotransferase, γ-glutamyltransferase, alpha-fetoprotein than those with a tumour size <5 cm (all P<0.05). We further revealed that the mtDNA content of HCC tumour tissues was 225.97(105.42, 430.54) [median (25th Percentile, 75th Percentile)] and was negatively correlated with 5-mC content (P = 0.035), but not 5-hmC content, in genomic DNA from HCC tumour tissues.

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Section: Discussionsupporting

confidence: 93%

Association of 5-Methylcytosine and 5-Hydroxymethylcytosine with Mitochondrial DNA Content and Clinical and Biochemical Parameters in Hepatocellular Carcinoma

Shen

Huang

et al. 2013

PLoS ONE

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“…Munnich [ 36 ] and Zhang [ 37 ] studied adult and child patients with mitochondrial disease and found lactic acidosis in >50% patients. In our study, lactic acidosis was found in approximately 30% of patients, which is similar to the results of a previous study of 235 children with mitochondrial diseases [ 38 ], and may represent the true prevalence of lactic acidosis in children [ 39 ]. We found that the ΔmtDNA 4977 proportion and copy number as well as the total mtDNA copy number were all correlated with lactic acidosis in the younger group, likely owing to the effects of this deletion on the lactate production pathway; however, this finding remains to be confirmed experimentally.…”

Section: Discussionsupporting

confidence: 91%

Deletion of a 4977-bp Fragment in the Mitochondrial Genome Is Associated with Mitochondrial Disease Severity

Zhang

et al. 2015

PLoS ONE

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Large deletions in mitochondrial DNA (mtDNA) may be involved in the pathogenesis of mitochondrial disease. In this study, we investigated the relationship between a 4,977-bp deletion in the mitochondrial genome (ΔmtDNA4977) and the severity of clinical symptoms in patients with mitochondrial disease lacking known point mutations. A total of 160 patients with mitochondrial disease and 101 healthy controls were recruited for this study. The copy numbers of ΔmtDNA4977 and wild-type mtDNA were determined by real-time quantitative PCR and analyzed using Spearman’s bivariate correlation analysis, t-tests, or one-way ANOVA. The overall ΔmtDNA4977 copy number per cell and the proportion of mtDNA4977 relative to the total wild-type mtDNA, increased with patient age and symptom severity. Surprisingly, the total mtDNA copy number decreased with increasing symptom severity. Our analyses revealed that increases in the proportion and total copy number of ΔmtDNA4977 in the blood may be associated with disease severity in patients with mitochondrial dysfunction.

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“…In addition, further study of muscle bioenergetics is needed in each of these disease conditions. Evidence suggests that mitochondrial DNA (mtDNA) is depleted in patients with both CKD and cirrhosis (Lim et al, 2000; Pesce et al, 2002), suggesting that impairments in muscular bioenergetic efficiency may contribute to the pathogenesis of uremic and/or hepatic myopathies.…”

Section: Disease-mediated Pathwaysmentioning

confidence: 99%

Models of accelerated sarcopenia: Critical pieces for solving the puzzle of age-related muscle atrophy

Buford¹,

Anton²,

Judge³

et al. 2010

Ageing Research Reviews

257

180

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Sarcopenia, the age-related loss of skeletal muscle mass, is a significant public health concern that continues to grow in relevance as the population ages. Certain conditions have the strong potential to coincide with sarcopenia to accelerate the progression of muscle atrophy in older adults. Among these conditions are co-morbid diseases common to older individuals such as cancer, kidney disease, diabetes, and peripheral artery disease. Furthermore, behaviors such as poor nutrition and physical inactivity are well-known to contribute to sarcopenia development. However, we argue that these behaviors are not inherent to the development of sarcopenia but rather accelerate its progression. In the present review, we discuss how these factors affect systemic and cellular mechanisms that contribute to skeletal muscle atrophy. In addition, we describe gaps in the literature concerning the role of these factors in accelerating sarcopenia progression. Elucidating biochemical pathways related to accelerated muscle atrophy may allow for improved discovery of therapeutic treatments related to sarcopenia.

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Depletion of mitochondrial DNA in the skeletal muscle of two cirrhotic patients with severe asthenia

Cited by 11 publications

References 31 publications

Association of 5-Methylcytosine and 5-Hydroxymethylcytosine with Mitochondrial DNA Content and Clinical and Biochemical Parameters in Hepatocellular Carcinoma

Association of 5-Methylcytosine and 5-Hydroxymethylcytosine with Mitochondrial DNA Content and Clinical and Biochemical Parameters in Hepatocellular Carcinoma

Deletion of a 4977-bp Fragment in the Mitochondrial Genome Is Associated with Mitochondrial Disease Severity

Models of accelerated sarcopenia: Critical pieces for solving the puzzle of age-related muscle atrophy

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