Catecholamines regulate the activity, secretion, and synthesis of renalase.

Catecholamines regulate the activity, secretion, and synthesis of renalase. Research Abstract Details 

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Catecholamines regulate the activity, secretion, and synthesis of renalase. Abstract Text:

Guoyong Li,Jianchao Xu,Peili Wang,Heino Velazquez,Yanyan Li,Yanling Wu,Gary V Desir,

BACKGROUND: We previously identified renalase, a secreted novel amine oxidase that specifically degrades circulating catecholamines. Parenteral administration of either native or recombinant renalase lowers blood pressure, heart rate, and cardiac contractility by metabolizing circulating catecholamines. Renalase plasma levels are markedly reduced in patients with chronic kidney disease. It is not known whether endogenous renalase contributes to the regulation of catecholamines. METHODS AND RESULTS: We show here that circulating renalase lacks significant amine oxidase activity under basal conditions (prorenalase) but that a brief surge of epinephrine lasting <2 minutes causes renalase activity to increase from 48+/-18 to 2246+/-98 arbitrary units (n=3; P<0.002). Enzyme activation is detectable within 30 seconds and sustained for at least 60 minutes. Analysis of epinephrine-mediated hemodynamic changes in normotensive rats indicates that prorenalase becomes maximally activated when systolic pressure increases by >5 mm Hg. The catecholamine surge also leads to a 2.8-fold increase in plasma renalase concentration. Cultured cells exposed to dopamine upregulate steady-state renalase gene expression by >10-fold. The time course of prorenalase activation is abnormal in rats with chronic kidney disease. CONCLUSIONS: These data identify a novel mechanism for the regulation of circulating catecholamines. In the renalase pathway, excess catecholamine facilitates the conversion of prorenalase, an inactive plasma amine oxidase, to renalase, which can degrade catecholamines. Excess catecholamines not only regulate the activation of prorenalase but also promote its secretion and synthesis. Because chronic kidney disease is associated with a number of systemic abnormalities, including activation of the sympathetic nervous system, increased catecholamines levels, cardiac hypertrophy, and hypertension, renalase replacement is an attractive therapeutic modality owing to its role in catecholamine metabolism.

Catecholamines regulate the activity, secretion, and synthesis of renalase. Publishing Authors By Initials

G Li,J Xu,P Wang,H Velazquez,Y Li,Y Wu,GV Desir,

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Catecholamines regulate the activity, secretion, and synthesis of renalase. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Circulation

VOLUME: 117

Page Numbers: 1277-82

Journal Abbreviation: Circulation

ISSN: 1524-4539

DAY: 25

MONTH: 02

YEAR: 2008

Catecholamines regulate the activity, secretion, and synthesis of renalase. Information

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LANGUAGE: eng

NlmUniqueID: 147763

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Grant and Affiliation Information for Catecholamines regulate the activity, secretion, and synthesis of renalase.

AFFILIATION: Department of Medicine, Yale School of Medicine, New Haven, CT 06520-8029, USA.

Country: United States

AGENCY: United States NIDDK

GRANT: DK48105B

ACRONYM: DK

MEDLINETA: Circulation

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