Hoyer-Allo, Karla Johanna Ruth, Spath, Martin Richard, Brodesser, Susanne, Zhu, Yiyi, Binz-Lotter, Julia, Hohne, Martin ORCID: 0000-0001-8698-5389, Bronneke, Hella, Bohl, Katrin ORCID: 0000-0003-3746-4047, Johnsen, Marc, Kubacki, Torsten, Kiefer, Katharina, Seufert, Lisa, Koehler, Felix Carlo ORCID: 0000-0001-9269-7420, Grundmann, Franziska, Hackl, Matthias J., Schermer, Bernhard ORCID: 0000-0002-5194-9000, Bruning, Jens, Benzing, Thomas ORCID: 0000-0003-0512-1066, Burst, Volker and Muller, Roman-Ulrich (2022). Caloric restriction reduces the pro-inflammatory eicosanoid 20-hydroxyeicosatetraenoic acid to protect from acute kidney injury. Kidney Int., 102 (3). S. 560 - 577. NEW YORK: ELSEVIER SCIENCE INC. ISSN 1523-1755

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Abstract

Acute kidney injury is a frequent complication in the clinical setting and associated with significant morbidity and mortality. Preconditioning with short-term caloric restriction is highly protective against kidney injury in rodent ischemia reperfusion injury models. However, the underlying mechanisms are unknown hampering clinical translation. Here, we examined the molecular basis of caloric restriction-mediated protection to elucidate the principles of kidney stress resistance. Analysis of an RNAseq dataset after caloric restriction identified Cyp4a12a, a cytochrome exclusively expressed in male mice, to be strongly downregulated after caloric restriction. Kidney ischemia reperfusion injury robustly induced acute kidney injury in male mice and this damage could be markedly attenuated by pretreatment with caloric restriction. In females, damage was significantly less pronounced and preconditioning with caloric restriction had only little effect. Tissue concentrations of the metabolic product of Cyp4a12a, 20-hydroxyeicosatetraenoic acid (20-HETE), were found to be significantly reduced by caloric restriction. Conversely, intraperitoneal supplementation of 20-HETE in preconditioned males partly abrogated the protective potential of caloric restriction. Interestingly, this effect was accompanied by a partial reversal of caloric restriction-induced changes in protein but not RNA expression pointing towards inflammation, endoplasmic reticulum stress and lipid metabolism. Thus, our findings provide an insight into the mechanisms underlying kidney protection by caloric restriction. Hence, understanding the mediators of preconditioning is an important prerequisite for moving towards translation to the clinical setting.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Hoyer-Allo, Karla Johanna RuthUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Spath, Martin RichardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brodesser, SusanneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zhu, YiyiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Binz-Lotter, JuliaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hohne, MartinUNSPECIFIEDorcid.org/0000-0001-8698-5389UNSPECIFIED
Bronneke, HellaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bohl, KatrinUNSPECIFIEDorcid.org/0000-0003-3746-4047UNSPECIFIED
Johnsen, MarcUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kubacki, TorstenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kiefer, KatharinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Seufert, LisaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Koehler, Felix CarloUNSPECIFIEDorcid.org/0000-0001-9269-7420UNSPECIFIED
Grundmann, FranziskaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hackl, Matthias J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schermer, BernhardUNSPECIFIEDorcid.org/0000-0002-5194-9000UNSPECIFIED
Bruning, JensUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Benzing, ThomasUNSPECIFIEDorcid.org/0000-0003-0512-1066UNSPECIFIED
Burst, VolkerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Muller, Roman-UlrichUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-662726
DOI: 10.1016/j.kint.2022.04.033
Journal or Publication Title: Kidney Int.
Volume: 102
Number: 3
Page Range: S. 560 - 577
Date: 2022
Publisher: ELSEVIER SCIENCE INC
Place of Publication: NEW YORK
ISSN: 1523-1755
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
ISCHEMIA-REPERFUSION INJURY; ARACHIDONIC-ACID; DIETARY RESTRICTION; CYP4A ISOFORMS; BETA-ESTRADIOL; NITRIC-OXIDE; 20-HETE; TESTOSTERONE; EXPRESSION; SEXMultiple languages
Urology & NephrologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/66272

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