Exercise and diabetes have opposite effects on the assembly and O-GlcNAc modification of the mSin3A/HDAC1/2 complex in the heart

Cardiovascular Diabetology

Original Investigation

Emily J Cox¹  Susan A Marsh² 

[1] Graduate Program in Nutrition and Exercise Physiology, College of Pharmacy, Washington State University, Spokane, WA, USA;Program in Nutrition and Exercise Physiology, College of Pharmacy, Washington State University, PO Box 1495, 99210-1495, Spokane, WA, USA;

关键词: Exercise;    Diabetes;    Cardiac hypertrophy;    O-GlcNAc;    Fetal genes;   

DOI  :  10.1186/1475-2840-12-101

 received in 2013-05-16, accepted in 2013-06-30,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundExercise causes physiological cardiac hypertrophy and benefits the diabetic heart. Mammalian switch-independent 3A (mSin3A) and histone deacetylases (HDACs) 1 and 2 regulate hypertrophic genes through associations with the DNA binding proteins repressor element-1 silencing transcription factor (REST) and O-linked β-N-acetylglucosamine transferase (OGT). O-linked β-N-acetylglucosamine (O-GlcNAc) is a glucose derivative that is chronically elevated in diabetic hearts, and a previous study showed that exercise reduces cardiac O-GlcNAc. We hypothesized that O-GlcNAc and OGT would physically associate with mSin3A/HDAC1/2 in the heart, and that this interaction would be altered by diabetes and exercise.Methods8-week-old type 2 diabetic db/db (db) and non-diabetic C57 mice were randomized to treadmill exercise or sedentary groups for 1 or 4 weeks.ResultsO-GlcNAc was significantly higher in db hearts and increased with exercise. Db hearts showed lower levels of mSin3A, HDAC1, and HDAC2 protein, but higher levels of HDAC2 mRNA and HDAC1/2 deacetylase activity. Elevated HDAC activity was associated with significantly blunted expression of α-actin and brain natriuretic peptide in db hearts. In sedentary db hearts, co-immunoprecipitation assays showed that mSin3A and OGT were less associated with HDAC1 and HDAC2, respectively, compared to sedentary C57 controls; however, exercise removed these differences.ConclusionsThese data indicate that diabetes and exercise oppositely affect interactions between pro-hypertrophic transcription factors, and suggest that an increase in total cardiac O-GlcNAc is a mechanism by which exercise benefits type 2 diabetic hearts.

【 授权许可】

CC BY   
© Cox and Marsh; licensee BioMed Central Ltd. 2013