HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 277, Issue 39, 35779-35782, September 27, 2002

This Article Full Text Full Text (PDF) All Versions of this Article: 277/39/35779    most recent C200303200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kwok, J. B. J. Articles by Kapoor, V. Search for Related Content PubMed PubMed Citation Articles by Kwok, J. B. J. Articles by Kapoor, V.

ACCELERATED PUBLICATION
A Missense Mutation in Kynurenine Aminotransferase-1 in Spontaneously Hypertensive Rats^*

John B. J. Kwok^§¶, Ranjna Kapoor^§, Takanari Gotoda^§**, Yasuhiko Iwamoto^**, Yoko Iizuka^§§, Nobuhiro Yamada^¶¶, Kim E. Isaacs, Virag V. Kushwaha, W. Bret Church, Peter R. Schofield^¶, and Vimal Kapoor

From the  Garvan Institute of Medical Research, Sydney, 2010 Australia,  Department of Pharmacology and Physiology, University of New South Wales, Sydney 2052, Australia, ^** Diabetes Center, Tokyo Women's Medical University, Tokyo 162-8666, Japan, ^§§ Department of Metabolic Diseases, University of Tokyo, Tokyo 113-8655, Japan, and ^¶¶ Department of Internal Medicine, University of Tsukuba, Tsukuba 305-8575, Japan

Spontaneously hypertensive rats (SHR) are the most extensively used animal model for genetic hypertension, increased stroke damage, and insulin resistance syndromes; however, the identification of target genes has proved difficult. SHR show elevated sympathetic nerve activity, and stimulation of the central blood pressure control centers with glutamate or nicotine results in exaggerated blood pressure responses, effects that appear to be genetically determined. Kynurenic acid, a competitive glutamate antagonist and a non-competitive nicotinic antagonist, can be synthesized in the brain by the enzyme kynurenine aminotransferase-1 (KAT-1). We have previously shown that KAT-1 activity is significantly reduced in SHR compared with normotensive Wistar Kyoto rats (WKY). Here we show that KAT-1 contains a missense mutation, E61G, in all the strains of SHR examined but not in any of the WKY or outbred strains. Previous studies on F2 rats from a cross of stroke-prone SHR and WKY have shown a suggestive level of linkage between elevated blood pressure and the KAT-1 locus on chromosome 3. In addition, the mutant enzyme expressed in Escherichia coli displays altered kinetics. This mutation may explain the enhanced sensitivity to glutamate and nicotine seen in SHR that may be related to an underlying mechanism of hypertension and increased sensitivity to stroke.

This article has been cited by other articles:

				J. E. Wiggins, M. Goyal, S. K. Sanden, B. L. Wharram, K. A. Shedden, D. E. Misek, R. D. Kuick, and R. C. Wiggins Podocyte Hypertrophy, "Adaptation," and "Decompensation" Associated with Glomerular Enlargement and Glomerulosclerosis in the Aging Rat: Prevention by Calorie Restriction J. Am. Soc. Nephrol., October 1, 2005; 16(10): 2953 - 2966. [Abstract] [Full Text] [PDF]

				F. Rossi, Q. Han, J. Li, J. Li, and M. Rizzi Crystal Structure of Human Kynurenine Aminotransferase I J. Biol. Chem., November 26, 2004; 279(48): 50214 - 50220. [Abstract] [Full Text] [PDF]