Effects of hyperglycemia and aging on nuclear sirtuins and DNA damage of mouse hepatocytes

Autor(es)

Ghiraldini, Flavia Gerelli ^[1] ; Vitolo Crispim, Ana Carolina ^[1] ; Silveira Mello, Maria Luiza ^[1]

Afiliação do(s) autor(es)

^[1] Univ Estadual Campinas, Inst Biol, Dept Struct & Funct Biol, BR-13083862 Campinas, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: MOLECULAR BIOLOGY OF THE CELL; v. 24, n. 15, p. 2467-2476, AUG 1 2013.
• Citações Web of Science: 15

Resumo

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-1 alpha 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. (AU)

• Processo FAPESP: 10/50015-6 - Estrutura e organização da cromatina com o envelhecimento e o diabetes frente a alterações induzidas em marcadores epigenéticos
• Beneficiário: Maria Luiza Silveira Mello
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 08/58067-5 - Efeitos do envelhecimento e do diabetes mellitus do tipo I sobre a estrutura da cromatina de hepatócitos de camundongos
• Beneficiário: Flávia Gerelli Ghiraldini
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto