Human alpha B-crystallin mutation causes oxido-reductive stress and protein aggregation cardiomyopathy in mice.

Human alpha B-crystallin mutation causes oxido-reductive stress and protein aggregation cardiomyopathy in mice. Research Abstract Details 

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Human alpha B-crystallin mutation causes oxido-reductive stress and protein aggregation cardiomyopathy in mice. Abstract Text:

The autosomal dominant mutation in the human alphaB-crystallin gene inducing a R120G amino acid exchange causes a multisystem, protein aggregation disease including cardiomyopathy. The pathogenesis of cardiomyopathy in this mutant (hR120GCryAB) is poorly understood. Here, we show that transgenic mice overexpressing cardiac-specific hR120GCryAB recapitulate the cardiomyopathy in humans and find that the mice are under reductive stress. The myopathic hearts show an increased recycling of oxidized glutathione (GSSG) to reduced glutathione (GSH), which is due to the augmented expression and enzymatic activities of glucose-6-phosphate dehydrogenase (G6PD), glutathione reductase, and glutathione peroxidase. The intercross of hR120GCryAB cardiomyopathic animals with mice with reduced G6PD levels rescues the progeny from cardiac hypertrophy and protein aggregation. These findings demonstrate that dysregulation of G6PD activity is necessary and sufficient for maladaptive reductive stress and suggest a novel therapeutic target for abrogating R120GCryAB cardiomyopathy and heart failure in humans.

Human alpha B-crystallin mutation causes oxido-reductive stress and protein aggregation cardiomyopathy in mice. Publishing Authors By Initials

For similar proteins: eye proteins: crystallins: alpha-crystallins: alpha-crystallin b chain research abstracts see: proteins: eye proteins: crystallins: alpha-crystallins: alpha-crystallin b chain research

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Human alpha B-crystallin mutation causes oxido-reductive stress and protein aggregation cardiomyopathy in mice. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Cell

VOLUME: 130

Page Numbers: 427-39

Journal Abbreviation: Cell

ISSN: 0092-8674

DAY: 10

MONTH: Aug

YEAR: 2007

Human alpha B-crystallin mutation causes oxido-reductive stress and protein aggregation cardiomyopathy in mice. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 413066

Human alpha B-crystallin mutation causes oxido-reductive stress and protein aggregation cardiomyopathy in mice. Keywords Mesh Terms:

KEYWORDS: alpha-Crystallin B Chain

MESH TERMS: physiology

Chemical & Substance for Abstract: Human alpha B-crystallin mutation causes oxido-reductive stress and protein aggregation cardiomyopathy in mice. Information

Substance Name: Glucosephosphate Dehydrogenase

Registry Number: EC 1.1.1.49

Grant and Affiliation Information for Human alpha B-crystallin mutation causes oxido-reductive stress and protein aggregation cardiomyopathy in mice.

AFFILIATION: Center for Cardiovascular Translational Biomedicine, Division of Cardiology, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT 84132, USA.

Country: United States

AGENCY: United States NHLBI

GRANT: 5R01 HL63874

ACRONYM: HL

MEDLINETA: Cell

REFSOURCE: Cell. 2007 Aug 10;130(3):401-2

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