Bioscience Reports

Angiopoietin-like 4: a decade of research

2012-06-01

The past decade has seen a rapid development and increasing recognition of ANGPTL4 (angiopoietin-like 4) as a remarkably multifaceted protein that is involved in many metabolic and non-metabolic conditions. ANGPTL4 has been recognised as a central player in various aspects of energy homoeostasis, at least in part, via the inhibitory interaction between the coiled-coil domain of ANGPTL4 and LPL (lipoprotein lipase). The fibrinogen-like domain of ANGPTL4 interacts and activates specific integrins to facilitate wound healing, modulates vascular permeability, and regulates ROS (reactive oxygen species) level to promote tumorigenesis. The present review summarizes these landmark findings about ANGPTL4 and highlights several important implications for future clinical practice. Importantly, these implications have also raised many questions that are in urgent need of further investigations, particularly the transcription regulation of ANGPTL4 expression, and the post-translation cleavage and modifications of ANGPTL4. The research findings over the past decade have laid the foundation for a better mechanistic understanding of the new scientific discoveries on the diverse roles of ANGPTL4.

Isolation and identification of a novel polysaccharide-peptide complex with antioxidant, anti-proliferative and hypoglycaemic activities from the abalone mushroom

2012-06-01

A novel antioxidant polysaccharide-peptide complex LB-1b from the fruiting bodies of the edible abalone mushroom (Pleurotus abalonus) was purified and identified. The structural characteristic of LB-1b was identified by FTIR (Fourier-transform IR), ¹³C NMR and ¹H NMR spectroscopy. LB-1b is a polysaccharide-peptide complex that contains glucose, rhamnose, glucuronic acid and galactose in the molar ratio of 22.4:1:1.7:1.6 and the N-terminal sequence of its peptide moiety has also been determined. The N-terminal amino acid sequence of LB-1b, IPKERKEFQQAQHLK, showed some resemblance to antioxidant enzymes. LB-1b exhibited high antioxidant activity in erythrocyte haemolysis in vitro and the anti-proliferative activity towards hepatoma HepG2 cells and breast cancer MCF7 cells with an IC₅₀ of 24 and 14 μM respectively. LB-1b also demonstrated hypoglycaemic activity in drug-induced diabetic mice and anti-HIV-1 RT (reverse transcriptase) with an IC₅₀ value of 12.5 μM.

Inactivation of the AMP-activated protein kinase by glucose in cardiac myocytes: a role for the pentose phosphate pathway

Ikhlass Tabidi and David Saggerson — 2012-06-01

Incubation of adult rat cardiac myocytes with increasing glucose concentrations decreased phosphorylation (αThr¹⁷²) and activity of AMPK (AMP-activated protein kinase). The effect could be demonstrated without measurable changes in adenine nucleotide contents. The glucose effect was additive to the decrease in AMPK activity caused by insulin, was attenuated by adrenaline, was not mimicked by glucose analogues, lactate or pyruvate and was not due to changes in myocyte glycogen content. AMPK activity was decreased by xylitol and PMS (phenazine methosulfate) and was increased by the glucose-6-phosphate dehydrogenase inhibitor DHEA (dehydroepiandrosterone) and by thiamine. PMS and DHEA respectively, increased and decreased CO₂ formation by the PPP (pentose phosphate pathway). AMPK activity was inversely related to the myocyte content of Xu5P (xylulose 5-phosphate), an intermediate of the non-oxidative arm of the PPP. Endothall, an inhibitor of PP2A (protein phosphatase 2A), abolished the glucose effect on AMPK activity. Further studies are needed to define the 'active component' that mediates the glucose effect and whether its site of action is PP2A.