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Decreased mitochondrial OGG1 expression is linked to mitochondrial defects and delayed hepatoma cell growth.

ABSTRACT: Many solid tumor cells exhibit mitochondrial respiratory impairment; however, the mechanisms of such impairment in cancer development remain unclear. Here, we demonstrate that SNU human hepatoma cells with declined mitochondrial respiratory activity showed decreased expression of mitochondrial 8-oxoguanine DNA glycosylase/lyase (mtOGG1), a mitochondrial DNA repair enzyme; similar results were obtained with human hepatocellular carcinoma tissues. Among several OGG1-2 variants with a mitochondrial-targeting sequence (OGG1-2a, -2b, -2c, -2d, and -2e), OGG1-2a was the major mitochondrial isoform in all examined hepatoma cells. Interestingly, hepatoma cells with low mtOGG1 levels showed delayed cell growth and increased intracellular reactive oxygen species (ROS) levels. Knockdown of OGG1-2 isoforms in Chang-L cells, which have active mitochondrial respiration with high mtOGG1 levels, significantly decreased cellular respiration and cell growth, and increased intracellular ROS. Overexpression of OGG1-2a in SNU423 cells, which have low mtOGG1 levels, effectively recovered cellular respiration and cell growth activities, and decreased intracellular ROS. Taken together, our results suggest that mtOGG1 plays an important role in maintaining mitochondrial respiration, thereby contributing to cell growth of hepatoma cells.

SUBMITTER: Lee YK

PROVIDER: S-EPMC3887880 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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Decreased mitochondrial OGG1 expression is linked to mitochondrial defects and delayed hepatoma cell growth.

Lee Young-Kyoung YK Youn Hwang-Guem HG Wang Hee-Jung HJ Yoon Gyesoon G

Molecules and cells 20130514 6

Many solid tumor cells exhibit mitochondrial respiratory impairment; however, the mechanisms of such impairment in cancer development remain unclear. Here, we demonstrate that SNU human hepatoma cells with declined mitochondrial respiratory activity showed decreased expression of mitochondrial 8-oxoguanine DNA glycosylase/lyase (mtOGG1), a mitochondrial DNA repair enzyme; similar results were obtained with human hepatocellular carcinoma tissues. Among several OGG1-2 variants with a mitochondrial ...[more]

PMID: 23677377

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Project description:Alfalfa (Medicago sativa L.) is an important forage in intercropping or rotation ecosystem, and shading is the principal limiting factor for its growth under the crop or forest. Agronomic studies showed that shading would systematically reduce the biomass of alfalfa. However, little is known about the reproduction of alfalfa under shading conditions. In order to study the effect of shading on the reproductive characteristics of alfalfa, two alfalfa cultivars (“Victoria” and “Eureka”) were used to study the effect of shading levels (full light, 56.4% shade, and 78.7% shade) on alfalfa flowering phenology, pollen viability, stigma receptivity, and seed quality. Results showed that shading delayed flowering phenology, shortened the flowering stage, faded the flower colors, and significantly reduced pollen viability, stigma receptivity, the number of flowers, quantity, and quality of seeds. Under shading conditions, seed yield per plant was obviously positively correlated with germination potential, germination rate, pollen viability, and 1,000-seed weight. The number of flower buds, pollen viability, 1,000-seed weight, and germination rate had the greatest positive direct impact on seed yield per plant. Our findings suggested that delayed flowering and reducing reproduction growth were important strategies for alfalfa to cope with shading and pollen viability was the key bottleneck for the success of alfalfa reproduction under shading. However, given that alfalfa is a perennial vegetative-harvest forage, delaying flowering in a weak light environment was beneficial to maintain the high aboveground biomass of alfalfa. Therefore, this should be taken into account when breeding alfalfa cultivars suitable for intercropping. Future research should further reveal the genetic and molecular mechanism of delayed flowering regulating the accumulation and distribution of assimilates between vegetative and reproductive organs of alfalfa under shading, so as to provide a theoretical basis for breeding of shade-tolerant alfalfa cultivars.

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Decreased mitochondrial OGG1 expression is linked to mitochondrial defects and delayed hepatoma cell growth.

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Decreased mitochondrial OGG1 expression is linked to mitochondrial defects and delayed hepatoma cell growth.

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