The relationship between serum asymmetric dimethylarginine levels and subjective sleep quality in normotensive patients with type 2 diabetes mellitus

BACKGROUND/AIMS: Poor sleep quality (SQ) is associated with increased cardiovascular mortality and morbidity. Additionally, asymmetric dimethylarginine (ADMA) is an independent predictor of cardiovascular mortality and morbidity. However, no sufficient data regarding the relationship between ADMA levels and SQ have been reported. The goal of the current study was to evaluate the association between SQ and ADMA levels in normotensive patients with type 2 diabetes mellitus. METHODS: The study participants consisted of 78 normotensive type 2 diabetics. The SQ of all participants was assessed using the Pittsburgh Sleep Quality Index (PSQI). Patients with a global PSQI score > 5 were defined as "poor sleepers." Factors associated with poor SQ were analyzed using a multiple regression model. Serum ADMA levels were measured using high performance liquid chromatography. RESULTS: The median ADMA levels of the poor sleepers were increased compared with patients defined as good sleepers (5.5 [4.2 to 6.6] vs. 4.4 [2.9 to 5.4], p < 0.01, respectively). However, the L-arginine/ADMA ratio was decreased in poor sleepers (p < 0.01). Global PSQI scores were positively correlated with ADMA levels (p < 0.01) and negatively correlated with the L-arginine/ADMA ratio (p = 0.02). ADMA levels were correlated with sleep latency (p < 0.01) and sleep efficiency (p = 0.01). Logistic regression analysis showed that ADMA levels (odds ratio [OR], 1.68; 95% confidence interval [CI], 1.16 to 2.44; p = 0.01) and body mass index (OR, 1.15; 95% CI, 1.01 to 1.31; p = 0.04) were associated with poor SQ independently of glomerular filtration rate, sex, age, duration of diabetes, hemoglobin A1c, total cholesterol, and systolic blood pressure. CONCLUSIONS: Self-reported SQ was independently associated with ADMA levels in normotensive patients with diabetes mellitus.

Methylation of eukaryotic elongation factor 2 induced by basic fibroblast growth factor via mitogen-activated protein kinase

Protein arginine methylation is important for a variety of cellular processes including transcriptional regulation, mRNA splicing, DNA repair, nuclear/cytoplasmic shuttling and various signal transduction pathways. However, the role of arginine methylation in protein biosynthesis and the extracellular signals that control arginine methylation are not fully understood. Basic fibroblast growth factor (bFGF) has been identified as a potent stimulator of myofibroblast dedifferentiation into fibroblasts. We demonstrated that symmetric arginine dimethylation of eukaryotic elongation factor 2 (eEF2) is induced by bFGF without the change in the expression level of eEF2 in mouse embryo fibroblast NIH3T3 cells. The eEF2 methylation is preceded by ras-raf-mitogen-activated protein kinase kinase (MEK)-extracellular signal-regulated kinase (ERK1/2)-p21(Cip/WAF1) activation, and suppressed by the mitogen-activated protein kinase (MAPK) inhibitor PD98059 and p21(Cip/WAF1) short interfering RNA (siRNA). We determined that protein arginine methyltransferase 7 (PRMT7) is responsible for the methylation, and that PRMT5 acts as a coordinator. Collectively, we demonstrated that eEF2, a key factor involved in protein translational elongation is symmetrically arginine-methylated in a reversible manner, being regulated by bFGF through MAPK signaling pathway.

Methylation of eukaryotic elongation factor 2 induced by basic fibroblast growth factor via mitogen-activated protein kinase

Protein arginine methylation is important for a variety of cellular processes including transcriptional regulation, mRNA splicing, DNA repair, nuclear/cytoplasmic shuttling and various signal transduction pathways. However, the role of arginine methylation in protein biosynthesis and the extracellular signals that control arginine methylation are not fully understood. Basic fibroblast growth factor (bFGF) has been identified as a potent stimulator of myofibroblast dedifferentiation into fibroblasts. We demonstrated that symmetric arginine dimethylation of eukaryotic elongation factor 2 (eEF2) is induced by bFGF without the change in the expression level of eEF2 in mouse embryo fibroblast NIH3T3 cells. The eEF2 methylation is preceded by ras-raf-mitogen-activated protein kinase kinase (MEK)-extracellular signal-regulated kinase (ERK1/2)-p21(Cip/WAF1) activation, and suppressed by the mitogen-activated protein kinase (MAPK) inhibitor PD98059 and p21(Cip/WAF1) short interfering RNA (siRNA). We determined that protein arginine methyltransferase 7 (PRMT7) is responsible for the methylation, and that PRMT5 acts as a coordinator. Collectively, we demonstrated that eEF2, a key factor involved in protein translational elongation is symmetrically arginine-methylated in a reversible manner, being regulated by bFGF through MAPK signaling pathway.