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(Circulation Research. 2007;101:1216.)
© 2007 American Heart Association, Inc.

Editorials

Searching for Causality of Knocking Out Txnip

Is Txnip Missing in Action?

Roger A. Davis

From the Department of Biology, BioScience Center, San Diego State University, Calif.

Correspondence to Prof Roger A. Davis, Director, Metabolic Research, Department of Biology, BioScience Center, Room 4104, San Diego State University, 5500 Campanile Dr, San Diego, CA 92182-4614. E-mail rdavis@sunstroke.sdsu.edu

See related article, pages 1328–1338

Key Words: Txnip • thioredoxin • PTEN • Akt • redox and cardiac glucose metabolism

An extract of the first 250 words of the full text is provided, because this article has no abstract.

	Introduction

 
Thioredoxin is an essential protein present in all known biological systems responsible for mediating the major pathway through which electrons are transferred from NADP(H) to protein disulfide bonds: NADP(H)+R-S-S-R'NADP+R-SH+HS-R'.^1,2 Thus, the discovery that thioredoxin-interacting protein (Txnip) bound to and inhibited thioredoxin–NADPH–dependent reduction of protein disulfides³ predicted that Txnip would both counter thioredoxin-mediated protection from oxidative stress^4–10 and have pleiotropic physiologic influence on process dependent on proteins containing disulfide determinants of structure/function. Elegant quantitative trait loci positional cloning identifying Txnip as the gene responsible for the hyperlipidemia associated with the murine Hyplip1 locus clearly supported this prediction.¹¹

In this issue of Circulation Research, Yoshioka et al¹² describe how gene-targeted disruption of Txnip influences the response of mice to transverse aortic constriction (TAC) (ie, Txnip knockout mice displayed improved cardiac function 4 weeks after TAC but decreased cardiac function after 8 weeks). The findings that Txnip deletion caused no change in thioredoxin enzyme activity, whereas cardiac glucose uptake in Txnip knockout mice was increased led the authors to conclude that Txnip does not simply act via regulating redox state, but rather it acts as a novel metabolic regulator.

This report provides several remarkably important insights regarding the function and targets of Txnip-thioredoxin.

	The Txnip Knockout Mouse Model

 
The 2007 awardees (Mario Capecchi, Martin Evans, and Oliver Smithies) of the Nobel Prize in Physiology and Medicine "for their discoveries of principles for introducing specific gene modifications in mice by the use of embryonic stem cells" emphasizes the enormous impact that gene targeting has had in providing . . . [Full Text of this Article]

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