Willmes, Diana M., Daniels, Martin, Kurzbach, Anica ORCID: 0000-0003-1531-3088, Lieske, Stefanie, Bechmann, Nicole ORCID: 0000-0002-6932-333X, Schumann, Tina, Henke, Christine, El-Agroudy, Nermeen N., Da Costa Goncalves, Andrey C., Peitzsch, Mirko, Hofmann, Anja, Kanczkowski, Waldemar ORCID: 0000-0002-5595-8393, Kraeker, Kristin, Mueller, Dominik N., Morawietz, Henning, Deussen, Andreas, Wagner, Michael, El-Armouche, Ali, Helfand, Stephen L., Bornstein, Stephan R., de Cabo, Rafael, Bernier, Michel ORCID: 0000-0002-5948-368X, Eisenhofer, Graeme ORCID: 0000-0002-8601-9903, Tank, Jens ORCID: 0000-0002-5672-1187, Jordan, Jens and Birkenfeld, Andreas L. (2021). The longevity gene mIndy (I'm Not Dead, Yet) affects blood pressure through sympathoadrenal mechanisms. JCI Insight, 6 (2). ANN ARBOR: AMER SOC CLINICAL INVESTIGATION INC. ISSN 2379-3708

Full text not available from this repository.

Abstract

Reduced expression of the plasma membrane citrate transporter INDY (acronym I'm Not Dead, Yet) extends life span in lower organisms. Deletion of the mammalian Indy (mIndy) gene in rodents improves metabolism via mechanisms akin to caloric restriction, known to lower blood pressure {BP) by sympathoadrenal inhibition. We hypothesized that mIady deletion attenuates sympathoadrenal support of BP. Continuous arterial BP and heart rate (HR) were reduced in mINDY-KO mice. Concomitantly, urinary catecholamine content was lower, and the decreases in BP and HR by mIndy deletion were attenuated after autonomic ganglionic blockade. Catecholamine biosynthesis pathways were reduced in mINDY-KO adrenals using unbiased microarray analysis. Citrate, the main mINDY substrate, increased catecholamine content in pheochromocytoma cells, while pharmacological inhibition of citrate uptake blunted the effect. Our data suggest that deletion of mIndy reduces sympathoadrenal support of BP and HR by attenuating catecholamine biosynthesis. Deletion of mIndy recapitulates beneficial cardiovascular and metabolic responses to caloric restriction, making it an attractive therapeutic target.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Willmes, Diana M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Daniels, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kurzbach, AnicaUNSPECIFIEDorcid.org/0000-0003-1531-3088UNSPECIFIED
Lieske, StefanieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bechmann, NicoleUNSPECIFIEDorcid.org/0000-0002-6932-333XUNSPECIFIED
Schumann, TinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Henke, ChristineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
El-Agroudy, Nermeen N.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Da Costa Goncalves, Andrey C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Peitzsch, MirkoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hofmann, AnjaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kanczkowski, WaldemarUNSPECIFIEDorcid.org/0000-0002-5595-8393UNSPECIFIED
Kraeker, KristinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mueller, Dominik N.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Morawietz, HenningUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Deussen, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wagner, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
El-Armouche, AliUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Helfand, Stephen L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bornstein, Stephan R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
de Cabo, RafaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bernier, MichelUNSPECIFIEDorcid.org/0000-0002-5948-368XUNSPECIFIED
Eisenhofer, GraemeUNSPECIFIEDorcid.org/0000-0002-8601-9903UNSPECIFIED
Tank, JensUNSPECIFIEDorcid.org/0000-0002-5672-1187UNSPECIFIED
Jordan, JensUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Birkenfeld, Andreas L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-603372
DOI: 10.1172/jci.insight.136083
Journal or Publication Title: JCI Insight
Volume: 6
Number: 2
Date: 2021
Publisher: AMER SOC CLINICAL INVESTIGATION INC
Place of Publication: ANN ARBOR
ISSN: 2379-3708
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
SYMPATHETIC-NERVOUS-SYSTEM; ATRIAL-NATRIURETIC-FACTOR; INSULIN SENSITIVITY; CALORIE RESTRICTION; FATTY LIVER; LIFE-SPAN; CATECHOLAMINES; METABOLISM; DIET; RESISTANCEMultiple languages
Medicine, Research & ExperimentalMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/60337

Downloads

Downloads per month over past year

Altmetric

Export

Actions (login required)

View Item View Item