Universität zu Köln

Rinschen, Markus M., Palygin, Oleg ORCID: 0000-0002-3680-5527, Guijas, Carlos ORCID: 0000-0001-7993-3388, Palermo, Amelia ORCID: 0000-0001-5705-6521, Palacio-Escat, Nicolas ORCID: 0000-0002-7022-1437, Domingo-Almenara, Xavier ORCID: 0000-0002-0133-6863, Montenegro-Burke, Rafael, Saez-Rodriguez, Julio ORCID: 0000-0002-8552-8976, Staruschenko, Alexander ORCID: 0000-0002-5190-8356 and Siuzdak, Gary ORCID: 0000-0002-4749-0014 (2019). Metabolic rewiring of the hypertensive kidney. Sci. Signal., 12 (611). WASHINGTON: AMER ASSOC ADVANCEMENT SCIENCE. ISSN 1937-9145

Full text not available from this repository.

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, glomeruli showed increased expression of metabolic enzymes of central carbon metabolism, amino acid degradation, and lipid oxidation, findings observed in previously published studies from other disease models and patients with glomerular damage. Overall, multilayered omics provides an overview of hypertensive kidney damage and suggests that metabolic or dietary interventions could prevent and treat glomerular disease and hypertension-induced nephropathy.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Rinschen, Markus M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Palygin, Oleg UNSPECIFIED orcid.org/0000-0002-3680-5527 UNSPECIFIED Guijas, Carlos UNSPECIFIED orcid.org/0000-0001-7993-3388 UNSPECIFIED Palermo, Amelia UNSPECIFIED orcid.org/0000-0001-5705-6521 UNSPECIFIED Palacio-Escat, Nicolas UNSPECIFIED orcid.org/0000-0002-7022-1437 UNSPECIFIED Domingo-Almenara, Xavier UNSPECIFIED orcid.org/0000-0002-0133-6863 UNSPECIFIED Montenegro-Burke, Rafael UNSPECIFIED UNSPECIFIED UNSPECIFIED Saez-Rodriguez, Julio UNSPECIFIED orcid.org/0000-0002-8552-8976 UNSPECIFIED Staruschenko, Alexander UNSPECIFIED orcid.org/0000-0002-5190-8356 UNSPECIFIED Siuzdak, Gary UNSPECIFIED orcid.org/0000-0002-4749-0014 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-124638
DOI:	10.1126/scisignal.aax9760
Journal or Publication Title:	Sci. Signal.
Volume:	12
Number:	611
Date:	2019
Publisher:	AMER ASSOC ADVANCEMENT SCIENCE
Place of Publication:	WASHINGTON
ISSN:	1937-9145
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language WEB SERVER; DISEASE; PHOSPHORYLATION; DYSFUNCTION; PODOCYTE; REVEALS; COMPLEX; SALT; UNRAVELS; PATHWAY Multiple languages Biochemistry & Molecular Biology; Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/12463