Effect of 7,8-dihydroneopterin mediated CD36 down regulation and oxidant scavenging on oxidised low-density lipoprotein induced cell death in human macrophages.

The role of CD36 in oxidised low-density lipoprotein (oxLDL) mediated cell death was examined by down regulating the receptor level with the macrophage generated antioxidant 7,8-dihydroneopterin. Down regulation of CD36 protein levels in human monocyte derived macrophages by 7,8-dihydroneopterin corresponded to a decrease in CD36-mRNA. The oxidation products of 7,8-dihydroneopterin, dihydroxanthopterin and neopterin did not significantly down regulate CD36. The CD36 down regulation resulted in a decrease in oxLDL uptake measured as 7-ketocholesterol accumulation. Though less oxLDL was taken up by the macrophages as a result of the 7,8-dihydroneopterin induced down regulation in CD36 levels, the cytotoxicity of the oxLDL was not decreased. Addition of 7,8-dihydroneopterin to oxLDL treated macrophages decreased the concentration of intracellular oxidants. In the presence of oxLDL, 7,8-dihydroneopterin was oxidised to neopterin showing that the 7,8-dihydroneopterin was scavenging intracellular oxidants generated in response to the oxLDL. The results show CD36 down regulation does not protect human macrophages form oxLDL cytotoxicity but 7,8-dihydroneopterin intracellular oxidant scavenging is protective.

Warming, CO2, and nitrogen deposition interactively affect a plant-pollinator mutualism.

Environmental changes threaten plant-pollinator mutualisms and their critical ecosystem service. Drivers such as land use, invasions and climate change can affect pollinator diversity or species encounter rates. However, nitrogen deposition, climate warming and CO(2) enrichment could interact to disrupt this crucial mutualism by altering plant chemistry in ways that alter floral attractiveness or even nutritional rewards for pollinators. Using a pumpkin model system, we show that these drivers non-additively affect flower morphology, phenology, flower sex ratios and nectar chemistry (sugar and amino acids), thereby altering the attractiveness of nectar to bumble bee pollinators and reducing worker longevity. Alarmingly, bees were attracted to, and consumed more, nectar from a treatment that reduced their survival by 22%. Thus, three of the five major drivers of global environmental change have previously unknown interactive effects on plant-pollinator mutualisms that could not be predicted from studies of individual drivers in isolation.