Effects of chronic liver diseases on mitochondrial DNA transcription and replication in human liver

Kotake, Katsuhiro; Nonami, Toshiaki; Kurokawa, Tsuyoshi; Nakao, Akimasa; Murakami, Taro; Shimomura, Yoshiharu

doi:10.1016/s0024-3205(99)00276-3

Cited by 7 publications

(3 citation statements)

References 20 publications

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“…Therefore, one possible explanation for the increased mitochondrial gene expression is stimulation of mitochondrial biogenesis by ROS. This is consistent with the finding that a proportion of the patients in the present study with chronic hepatitis and alcoholic liver disease also showed an increase in mtTFA and NRF-1 to the same level as in PBC [31]. In addition, mtDNA is particularly susceptible to mutation [32].…”

Section: Discussionsupporting

confidence: 93%

Enhancement of mitochondrial gene expression in the liver of primary biliary cirrhosis

Chen

Nagayama

Enomoto

et al. 2005

Hepatology Research

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Section: Discussionsupporting

confidence: 93%

Enhancement of mitochondrial gene expression in the liver of primary biliary cirrhosis

Chen

Nagayama

Enomoto

et al. 2005

Hepatology Research

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“…Levels of hepatic injury markers were associated with serum folate levels ( 26 , 44 ) . Similarly, an increase in liver injuries from chronic hepatitis to cirrhosis impaired the mt respiratory activity and mtDNA replication in human liver ( 45 ) . We found that mtDNA deletions correlated with markers of liver dysfunction (GOT and GPT) levels of the studied subjects ( P < 0·05).…”

Section: Discussionmentioning

confidence: 99%

Lymphocytic mitochondrial DNA deletions, biochemical folate status and hepatocellular carcinoma susceptibility in a case–control study

Kuo

Lin

et al. 2009

Br J Nutr

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Mitochondrial (mt) DNA deletions and low folate status, proposed characteristics of carcinogenesis, in relation to human hepatocellular carcinoma (HCC) susceptibility are not clearly understood. We hypothesised that low folate status may modify frequencies of mtDNA deletions in humans, both of which could predispose individuals to HCC development. Biochemical folate status of serum and lymphocytes, and frequencies of mtDNA deletions in lymphocytes were determined in ninety HCC cases and ninety cancer-free healthy controls, individually matched by age and sex. The data revealed that HCC patients had lower levels of serum folate (P¼0·0002), lymphocytic folate (P¼ 0·040) and accumulated higher frequency of lymphocytic mtDNA deletions (P,0·0001) than the controls. In the total studied subjects, frequencies of lymphocytic mtDNA deletions were associated with hepatitic B infection (P¼ 0·004) and HCC incidents (P¼ 0·001), and were correlated with serum folate (r 20·155; P¼ 0·041), lymphocyte folate (r 2 0·314; P¼ 0·0001), levels of glutamate-oxaloacetate transaminase (GOT) (r 0·206; P¼0·006), glutamate-pyruvate transaminase (GPT) (r 0·163; P¼ 0·037) and a-fetal protein concentrations (r 0·212; P¼ 0·005). After adjustment for age, sex, lifestyle and one-carbon metabolite factors, individuals with low blood folate (, 11·5 nmol/l) or high mtDNA deletions (D threshold cycle number (C t ) . 5·3) had increased risks for HCC (OR 7·7, 95 % CI 1·9, 29·9, P¼ 0·003; OR 5·4; 95 % CI 1·7, 16·8, P¼0·003, respectively). When combined with folate deficiency (serum folate , 14 nmol/l), the OR of HCC in individuals with high levels of lymphocytic mtDNA deletions was enhanced (OR 13·3; 95 % CI 1·45, 122; P¼0·008). Further controlling for GOT and GPT levels, however, negated those effects on HCC risk. Taken together, the data suggest that biochemical folate status and liver injuries are important modulators to lymphocytic mtDNA deletions. The mt genetic instability that results from a high rate of mtDNA deletions and/or low folate status increased the risk for HCC, which is mediated by clinical hepatic lesions.

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“…Diminished mitochondrial number in tumor cells was also observed and was thought related to enhanced catabolism of mitochondrial proteins. The common 4977 bp deletion has also been found in hepatocellular carcinomas but at a lower level as compared to normal liver tissue (25). Increased levels of mtDNA-encoded transcripts for ND5, cytochrome c oxidase II, and 16S rRNA were detected in chemically induced rat hepatomas compared to normal hepatocytes.…”

Section: Mitochondrial Dna Aberrations In Solid Tumorsmentioning

confidence: 97%

Mitochondrial DNA Alterations in Cancer

Copeland

Wachsman

Johnson

et al. 2002

Cancer Investigation

207

113

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A number of studies have demonstrated the presence of mitochondrial DNA (mtDNA) mutations in cancer cells. In this article, we review mitochondrial genomic aberrations reported in solid tumors of the breast, colon, stomach, liver, kidney, bladder, head/neck, and lung. The tantalizing association of tumors with mtDNA mutations implicates these mutations in the process of carcinogenesis. Alterations in expression of mtDNA transcripts in a variety of cancer types are also reviewed. In solid tumors, elevated expression of mtDNA-genes coding for subunits of the mitochondrial electron respiratory chain may reflect mitochondrial adaptation to perturbations in cellular energy requirements. The role of mtDNA mutations and altered expression of mitochondrial genes in carcinogenesis is discussed. Mitochondrial DNA mutations can initiate a cascade of events leading to a continuous increase in the production of reactive oxygen species (persistent oxidative stress), a condition that probably favors tumor development.

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Effects of chronic liver diseases on mitochondrial DNA transcription and replication in human liver

Cited by 7 publications

References 20 publications

Enhancement of mitochondrial gene expression in the liver of primary biliary cirrhosis

Enhancement of mitochondrial gene expression in the liver of primary biliary cirrhosis

Lymphocytic mitochondrial DNA deletions, biochemical folate status and hepatocellular carcinoma susceptibility in a case–control study

Mitochondrial DNA Alterations in Cancer

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