Megalin/LRP2 Expression Is Induced by Peroxisome Proliferator-Activated Receptor -Alpha and -Gamma: Implications for PPARs' Roles in Renal Function

BACKGROUND: Megalin is a large endocytic receptor with relevant functions during development and adult life. It is expressed at the apical surface of several epithelial cell types, including proximal tubule cells (PTCs) in the kidney, where it internalizes apolipoproteins, vitamins and hormones with their corresponding carrier proteins and signaling molecules. Despite the important physiological roles of megalin little is known about the regulation of its expression. By analyzing the human megalin promoter, we found three response elements for the peroxisomal proliferator-activated receptor (PPAR). The objective of this study was to test whether megalin expression is regulated by the PPARs. METHODOLOGY/PRINCIPAL FINDINGS: Treatment of epithelial cell lines with PPARα or PPARγ ligands increased megalin mRNA and protein expression. The stimulation of megalin mRNA expression was blocked by the addition of specific PPARα or PPARγ antagonists. Furthermore, PPAR bound to three PPAR response elements located in the megalin promoter, as shown by EMSA, and PPARα and its agonist activated a luciferase construct containing a portion of the megalin promoter and the first response element. Accordingly, the activation of PPARα and PPARγ enhanced megalin expression in mouse kidney. As previously observed, high concentrations of bovine serum albumin (BSA) decreased megalin in PTCs in vitro; however, PTCs pretreated with PPARα and PPARγ agonists avoided this BSA-mediated reduction of megalin expression. Finally, we found that megalin expression was significantly inhibited in the PTCs of rats that were injected with BSA to induce tubulointerstitial damage and proteinuria. Treatment of these rats with PPARγ agonists counteracted the reduction in megalin expression and the proteinuria induced by BSA. CONCLUSIONS: PPARα/γ and their agonists positively control megalin expression. This regulation could have an important impact on several megalin-mediated physiological processes and on pathophysiologies such as chronic kidney disease associated with diabetes and hypertension, in which megalin expression is impaired

Short-Lived Trace Gases in the Surface Ocean and the Atmosphere

The two-way exchange of trace gases between the ocean and the atmosphere is important for both the chemistry and physics of the atmosphere and the biogeochemistry of the oceans, including the global cycling of elements. Here we review these exchanges and their importance for a range of gases whose lifetimes are generally short compared to the main greenhouse gases and which are, in most cases, more reactive than them. Gases considered include sulphur and related compounds, organohalogens, non-methane hydrocarbons, ozone, ammonia and related compounds, hydrogen and carbon monoxide. Finally, we stress the interactivity of the system, the importance of process understanding for modeling, the need for more extensive field measurements and their better seasonal coverage, the importance of inter-calibration exercises and finally the need to show the importance of air-sea exchanges for global cycling and how the field fits into the broader context of Earth System Science

Possible Chemical Transformations in Snow and Ice Induced by Solar (UV PHOTONS) and Cosmic Irradiation (MUONS)

Over the last decade there has been a growing interest in the chemical composition of the snow packs in the polar regions (Bales and Wolff, 1995). Delmas (Delmas, 1992; Delmas, 1994) has noted that “information recorded in polar ice cores over the last several hundred millennia is invaluable to studies aimed at understanding the pre-industrial environmental system and anticipating the future evolution of the climate and the atmosphere.” For example, the isotopic composition of the ice (H_2O) matrix is a reliable paleothermometer. From the analysis of deep Antarctic and Greenland ice cores the ice age environmental conditions appeared to correspond to about 6 °C cooler temperatures and atmospheric CO_2 and CH_4 levels lower by factors of nearly 2 and 4, respectively. The biogeochemical cycles of S and N also appear to be affected by climatic changes that result in modifications in the source intensity and the transport of gaseous precursors. Even though atmospheric sulfate is derived principally from marine biogenic sources (i.e., dimethyl sulfide emission), cataclysmic volcanic eruptions can contribute sporadically to the atmospheric sulfur budget through large point source emissions of SO_2. These events are ultimately detected in polar ice as H_2SO_4 spikes. Nitrate, which is the next most abundant anion found in polar snowfall, exhibits concentration changes that are poorly understood, but which could be linked with the polar ozone hole formation. In addition to ions derived primarily from gas-to-particle conversions, continental dust and sea-spray aerosol components are also present in the ice at much higher concentrations during ice ages than during interglacial periods due to an intensification of their production and long range transport under glacial climatic conditions