Description
Chronic and binge ethanol consumption in humans and in animal models has been associated with the induction of injury (such as fibrosis and scarring) in the liver as well as the intestine, brain, lung and immune system. The effects of chronic ethanol consumption on the human kidney are protective as seen in large population studies are controversial with the preponderance of the data suggesting protection less so than injury. The most recent meta-analysis was by Konig et al (2015) who studied 5476 participants aged 2875 years from the Prevention of Renal and Vascular End-Stage Disease (PREVEND) study to assess associations between alcohol consumption and risk of chronic kidney disease (CKD). They found in this population-based cohort, alcohol consumption was inversely associated with the risk of developing CKD. The protective effects of ethanol on the kidney present a unique model system to develop new hypothesis on protection against end organ damage by fibrosis. The data on the effects of alcohol or alcohol consumption at the molecular level on renal parenchyma are sparse. In cell culture and animal models chronic ethanol exposure has been show to induce protein post-translational modification (acetylation), protein expression (upregulation of cytochrome P450 CYP2E1 and local platelet-activating factor receptor (PAFR) ligand formation) as well as neutrophil infiltration and activation. Since hepatocytes do not express PAFR, these data suggest that the response of the kidney to chronic alcohol consumption is distinct from that of the liver or lung. Therefore, we hypothesized that mechanisms of ethanol-induced renal injury or protection are regulated by a protein signaling networks (PSN) modulated acutely by the phosphoproteome and long term epigenetically by the acetylproteome. To address this hypothesis we have initiated a tiered proteomics study to determine the effects of chronic alcohol consumption on the murine kidney and with a secondary insult of acute exposure of lipopolysaccharide (LPS) on the renal proteome, phosphoproteome and the acetylproteome. Data have already been collected on the total proteome and the phosphoproteome using a multiplexing approach. Data will be collected early spring on the acetylproteome.
Overall Design
Kidneys from mice exposed to a two-hit model of 6 week Lieber-DeCarli ethanol exposure with and without lipopolysaccharide (LPS) injection 4h prior to sacrifice were collected for RNA analysis. The study involved four conditions: pair fed control (PF), pair fed control with lipopolysaccharide injection 4hr prior to sacrifice (PF4hLPS), ethanol exposure (EtOH), and ethanol exposure with lipopolysaccharide injection 4hr prior to sacrifice (EtOH4hLPS). The comparisons made included PF4hLPS vs. PF; EtOH4hLPS vs EtOH; EtOH4hLPS vs PF4hLPS; EtOH vs PF, and EtOH AND EtOH4hLPS vs PF AND PF4hLPS.
Curator
mj_li