Back to Search
Start Over
Effects of hyperglycemia and aging on nuclear sirtuins and DNA damage of mouse hepatocytes
- Source :
- Molecular Biology of the Cell
- Publication Year :
- 2013
-
Abstract
- In normal aging, nuclear sirtuin levels decline and specific histone acetylation increases. In diabetic mice, Sirt1 and Sirt6 levels increase, which may induce gluconeogenesis through the PGC-1α pathway and DNA repair of the oxidative damage caused by hyperglycemia.<br />Hyperglycemia, like aging, induces chromatin remodeling in mouse hepatocytes in comparison to normoglycemia and younger age, respectively. Changes in glucose metabolism also affect the action and expression of sirtuins, promoting changes in chromatin conformation and dynamics. Here we investigate the abundance and activity of the nuclear sirtuins Sirt1, Sirt6, and Sirt7 in mouse hepatocytes in association with specific histone acetylation, DNA damage, and the activation of nucleolar organizing regions (NORs) in hyperglycemic nonobese diabetic (NOD) and old normoglycemic BALB/c mouse strains. Higher levels of Sirt1 and PGC-1α and increased expression of gluconeogenesis pathway genes are found in the hyperglycemic NOD mice. Increased Sirt6 abundance is found in the hyperglycemic NOD mice, which might increase DNA damage repair. With aging, lower Sirt1 abundance and activity, increased acetylated histone modifications and Sirt7 levels, and NOR methylation are found. Thus, whereas in normal aging cell metabolism is reduced, in the diabetic mice a compensatory mechanism may elevate Sirt1 and Sirt6 levels, increasing gluconeogenesis and DNA repair from the oxidative damage caused by hyperglycemia. Therefore understanding the regulation of epigenetic factors in diabetes and aging is crucial for the development of new therapeutic approaches that could prevent diseases and improve quality of life.
- Subjects :
- SIRT6
medicine.medical_specialty
Aging
DNA Repair
DNA repair
DNA damage
Nod
DNA Fragmentation
Biology
Chromatin remodeling
Epigenesis, Genetic
Histones
Mice
Sirtuin 1
Mice, Inbred NOD
Internal medicine
medicine
Nucleolus Organizer Region
Animals
Sirtuins
Epigenetics
Molecular Biology
NOD mice
Cell Nucleus
Mice, Inbred BALB C
Nuclear Functions
Gluconeogenesis
Acetylation
Antigens, Nuclear
Cell Biology
Articles
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
Oxidative Stress
Endocrinology
Histone
Biochemistry
Liver
Hyperglycemia
biology.protein
Hepatocytes
Female
Protein Processing, Post-Translational
Transcription Factors
Subjects
Details
- ISSN :
- 19394586
- Volume :
- 24
- Issue :
- 15
- Database :
- OpenAIRE
- Journal :
- Molecular biology of the cell
- Accession number :
- edsair.doi.dedup.....7180a92d6064fcd8cdc15d420d843dfe