Metabolic rewiring of the hypertensive kidney.

Metabolic rewiring of the hypertensive kidney. Sci Signal. 2019 Dec 10;12(611): Authors: Rinschen MM, Palygin O, Guijas C, Palermo A, Palacio-Escat N, Domingo-Almenara X, Montenegro-Burke R, Saez-Rodriguez J, Staruschenko A, Siuzdak G Abstract Hypertension is a persistent epidemic across the developed world that is closely associated with kidney disease. Here, we applied a metabolomic, phosphoproteomic, and proteomic strategy to analyze the effect of hypertensive insults on kidneys. Our data revealed the metabolic aspects of hypertension-induced glomerular sclerosis, including lipid breakdown at early disease stages and activation of anaplerotic pathways to regenerate energy equivalents to counter stress. For example, branched-chain amino acids and proline, required for collagen synthesis, were depleted in glomeruli at early time points. Furthermore, indicators of metabolic stress were reflected by low amounts of ATP and NADH and an increased abundance of oxidized lipids derived from lipid breakdown. These processes were specific to kidney glomeruli where metabolic signaling occurred through mTOR and AMPK signaling. Quantitative phosphoproteomics combined with computational modeling suggested that these processes controlled key molecules in glomeruli and specifically podocytes, including cytoskeletal components and GTP-binding proteins, which would be expected to compete for decreasing amounts of GTP at early time points. As a result...
Source: Science Signaling - Category: Biomedical Science Authors: Tags: Sci Signal Source Type: research