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1.
Int J Radiat Biol ; 93(12): 1334-1342, 2017 12.
Article in English | MEDLINE | ID: mdl-29063809

ABSTRACT

PURPOSE: To investigate the late effects of thoracic region irradiation (TRI) on mouse body weight. MATERIALS AND METHODS: Female C57BL/6 mice were divided into nonirradiated, 5 Gy total body irradiation, 9 Gy sub-total body irradiation, and 12.5 Gy thoracic region irradiation (TRI) groups. Changes in mouse weight were monitored every other week at similar time points for 12 months. The anatomical characteristics of abdominal visceral fat distribution were recorded, and mitochondrial DNA copy number in the hearts and livers and lipid metabolic signaling in the liver were analyzed. Data were analyzed by one-way analysis of variance and a student's t-test. RESULTS: TRI led to a significant increase (p < .001) in body weight that was dependent on time and individuals [42.1% of mice were overweight (50% increase in body weight) 4 months post-TRI and 100% of mice were overweight at 10 months post-TRI]. Gross anatomical features of abdominal visceral fat distribution and storage in radiation-induced overweight/severely overweight mice were similar to those of high fat diet-induced overweight/severely overweight mice. The mitochondrial genome of heart and liver tissues from overweight/severely overweight mice had significantly (p < .05) decreased functional mitochondrial DNA copy number (ratios decreased from 1 to 0.71 or 0.49, respectively) and significantly (p < .05) increased mitochondrial DNA mutations (ratios increased from 1 to 3.21 or 1.83, respectively). CPT1 and IRS2 lipid metabolic signaling was significantly (p < .05-.01) decreased for both mRNA (fold decrease from 1 to 0.60 or 0.55, respectively) and protein (fold decrease from 1 to 0.62 or 0.19, respectively). CONCLUSIONS: TRI can cause mice to gain weight. These findings indicate that TRI can result in lipid metabolic abnormalities and provide a model to study the factors that result in these abnormalities.


Subject(s)
Gamma Rays/adverse effects , Obesity/etiology , Thorax/radiation effects , Animals , Body Weight/radiation effects , Disease Progression , Female , Genome, Mitochondrial/radiation effects , Lipid Metabolism/radiation effects , Mice , Mice, Inbred C57BL , Obesity/genetics , Obesity/metabolism , Obesity/physiopathology
2.
PLoS Genet ; 9(9): e1003769, 2013.
Article in English | MEDLINE | ID: mdl-24039606

ABSTRACT

The pathogenic fungus Cryptococcus neoformans uses the Bwc1-Bwc2 photoreceptor complex to regulate mating in response to light, virulence and ultraviolet radiation tolerance. How the complex controls these functions is unclear. Here, we identify and characterize a gene in Cryptococcus, UVE1, whose mutation leads to a UV hypersensitive phenotype. The homologous gene in fission yeast Schizosaccharomyces pombe encodes an apurinic/apyrimidinic endonuclease acting in the UVDE-dependent excision repair (UVER) pathway. C. neoformans UVE1 complements a S. pombe uvde knockout strain. UVE1 is photoregulated in a Bwc1-dependent manner in Cryptococcus, and in Neurospora crassa and Phycomyces blakesleeanus that are species that represent two other major lineages in the fungi. Overexpression of UVE1 in bwc1 mutants rescues their UV sensitivity phenotype and gel mobility shift experiments show binding of Bwc2 to the UVE1 promoter, indicating that UVE1 is a direct downstream target for the Bwc1-Bwc2 complex. Uve1-GFP fusions localize to the mitochondria. Repair of UV-induced damage to the mitochondria is delayed in the uve1 mutant strain. Thus, in C. neoformans UVE1 is a key gene regulated in response to light that is responsible for tolerance to UV stress for protection of the mitochondrial genome.


Subject(s)
Cryptococcus neoformans/drug effects , Endodeoxyribonucleases/genetics , Genome, Mitochondrial/genetics , Hypersensitivity/genetics , Schizosaccharomyces pombe Proteins/genetics , Cryptococcus neoformans/genetics , Cryptococcus neoformans/radiation effects , DNA Damage/radiation effects , DNA, Fungal/genetics , DNA, Fungal/radiation effects , Endodeoxyribonucleases/metabolism , Gene Knockout Techniques , Genome, Mitochondrial/radiation effects , Mutation , Neurospora crassa/genetics , Neurospora crassa/radiation effects , Phycomyces/genetics , Phycomyces/radiation effects , Schizosaccharomyces/genetics , Schizosaccharomyces/radiation effects , Schizosaccharomyces pombe Proteins/metabolism , Ultraviolet Rays
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