Rabbit Anti-Human PDK1 Polyclonal Antibody

Vascular complications from diabetes often result in poor outcomes for patients, even after optimized interventions. Forkhead box protein O1 (FoxO1) is a key regulator of cellular metabolism and plays an important role in vessel formation and maturation. Alterations of FoxO1 occur in the cardiovascular system in diabetes, yet the role of FoxO1 in diabetic vascular complications is poorly understood. In Streptozotocin (STZ)-induced type 1 diabetic rats, FoxO1 expression was up-regulated in carotid arteries at 8 weeks of diabetes that was accompanied with adverse vascular remodelling characterized as increased wall thickness, carotid medial cross-sectional area, media-to-lumen ratio and decreased carotid artery lumen area. This adverse vascular remodelling induced by hyperglycaemia in diabetic rats required FoxO1 activation as pharmacological inhibition of FoxO1 with 50mg/kg AS1842856 (AS) reversed vascular remodelling in type 1 diabetic rats. The adverse vascular remodelling in type 1 diabetes mellitus (T1DM) occurred concomitantly with increases in pro-inflammatory factors, adhesion factors, apoptosis, NOD-like receptor family protein-3 inflammasome activation and the phenotypic switch of arterial smooth muscle cells, which were all reversed by AS. In addition, FoxO1 inhibition counteracted the down-regulation of its upstream mediator PDK1 in T1DM. PDK1 activator reduced FoxO1 nuclear translocation, which serves as the basis for subsequent transcriptional regulation during hyperglycaemia. Taken together, our data suggest that FoxO1 is a critical trigger for type 1 diabetes-induced vascular remodelling in rats, and inhibition of FoxO1 thus offers a potential therapeutic option for diabetes-associated cardiovascular diseases.

Purpose: To investigate the effect and mechanism of miR-646 on aerobic glycolysis and cell proliferation in nasopharyngeal carcinoma. Methods: MiR-646 expression in human nasopharyngeal carcinoma cell lines was determined by quantitative real-time polymerase chain reaction) (qRT-PCR). Cell counting kit-8 (CCK8) was used to evaluate cell viability, and colony formation assay was also performed. The target of miR-646 was determined by luciferase activity assay. The effect of miR-646 on aerobic glycolysis was assessed via glucose uptake, and lactate and ATP production. Western blot analysis was conducted to unravel the underlying mechanism involved in the regulation of miR-646 in nasopharyngeal carcinoma. Results: MiR-646 was downregulated in human nasopharyngeal carcinoma cell lines. MiR-646 mimics decreased cell viability and inhibited cell proliferation, whereas miR-646 inhibitor increased cell viability and promoted cell proliferation. Pyruvate dehydrogenase kinase 1(PDK1) was identified as a target of miR-646, and its expression was negatively regulated by miR-646. MiR-646 probably inhibited aerobic glycolysis via regulation of PDK1, as shown by decreased glucose uptake and decreased lactate and ATP production. The inhibitory effect of miR-646 on nasopharyngeal carcinoma cell proliferation was partly via PDK1 regulation. Conclusion: MiR-646 inhibits aerobic glycolysis in nasopharyngeal carcinoma and promotes cell proliferation via suppression of PDK1, suggesting miR-646 as a potential therapeutic target in nasopharyngeal carcinoma.