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Polyploidy and chromatin remodeling in hepatocytes from insulin-dependent diabetic and normoglycemic aged mice
- Source :
- Cytometry Part A. :755-764
- Publication Year :
- 2012
- Publisher :
- Wiley, 2012.
-
Abstract
- Changes in polyploidization, chromatin supraorganization, and chromatin accessibility were investigated in hepatocytes collected from adult, nonobese diabetic (NOD) mice with increasing hyperglycemia and compared with adult normoglycemic controls and 56-week-old normoglycemic BALB/c mice. Our goal was to determine the changes in ploidy degrees and chromatin characteristics in mouse hepatocytes that are associated with insulin-dependent diabetes and to detect similarities in these aspects with those verified with aging, with greater accuracy than previous studies. Image analysis of Feulgen-stained nuclei revealed changes in ploidy degrees and chromatin supraorganization. Chromatin accessibility was assessed with micrococcal nuclease (MNase) digestion. Increased polyploidy was associated with increasing levels of glycemia, and this trend toward polyploidy was found even under normoglycemic conditions in NOD mice. Although high degrees of ploidy were also detected in aged BALB/c mice, the magnitude of polyploidy was not the same magnitude as that in the diabetic mice. While there was increased homogeneity of chromatin packaging with increasing polyploidy under conditions of severe hyperglycemia (and even under conditions of normoglycemia) in NOD mice, an inverse relationship was observed in aged BALB/c mice. Chromatin accessibility to MNase increased under severe hyperglycemia and advanced age, but it was much higher in the diabetic mice. In conclusion, although similarities in polyploidy were observed between the hepatocytes from increasingly hyperglycemic adult mice and those from normoglycemic aged mice, the relationship between chromatin remodeling and increases in ploidy degrees was not the same between the hepatocytes of these two groups. These findings demonstrate that strict similarities between diabetes and aging are not always true at the cellular level. This discordance is likely due to differences in the metabolic state of mouse hepatocytes during aging and diabetic conditions consequent to specificities in their gene regulatory programs.
- Subjects :
- Blood Glucose
Aging
medicine.medical_specialty
Histology
Nod
Chromatin remodeling
Pathology and Forensic Medicine
Polyploidy
Mice
Mice, Inbred NOD
Internal medicine
Diabetes mellitus
Image Processing, Computer-Assisted
Rosaniline Dyes
medicine
Animals
Micrococcal Nuclease
DNA Cleavage
Coloring Agents
Gene
NOD mice
Mice, Inbred BALB C
biology
DNA
Cell Biology
Chromatin Assembly and Disassembly
medicine.disease
Chromatin
Diabetes Mellitus, Type 1
Endocrinology
Immunology
Hepatocytes
biology.protein
Female
Ploidy
Micrococcal nuclease
Subjects
Details
- ISSN :
- 15524922
- Database :
- OpenAIRE
- Journal :
- Cytometry Part A
- Accession number :
- edsair.doi.dedup.....cd4d443d54285fc9ef8c4f157c326113