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J. Biol. Chem., Vol. 277, Issue 5, 3274-3279, February 1, 2002
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From the Recent studies have shown that trehalose plays a
protective role in yeast in a variety of stresses, including heat,
freezing and thawing, dehydration, hyperosmotic shock, and oxidant
injury. Because (a) heat shock and anoxia share mechanisms
that allow organisms to survive, (b) Drosophila
melanogaster is tolerant to anoxia, and (c) trehalose
is present in flies and is metabolically active, we asked whether
trehalose can protect against anoxic stress. Here we report on a new
role of trehalose in anoxia resistance in Drosophila. We
first cloned the gene trehalose-6-phosphate synthase
(tps1), which synthesizes trehalose, and examined the effect of tps1 overexpression as well as mutation on the
resistance of Drosophila to anoxia. Upon induction of
tps1, trehalose increased, and this was associated with
increased tolerance to anoxia. Furthermore, in vitro
experiments showed that trehalose reduced protein aggregation caused by
anoxia. Homozygous tps1 mutant (P-element insertion into
the third intron of the gene) leads to lethality at an early larval
stage, and excision of the P-element rescues totally the phenotype. We
conclude that trehalose contributes to anoxia tolerance in flies; this
protection is likely to be due to a reduction of protein aggregation.
Role of Trehalose Phosphate Synthase in Anoxia Tolerance and
Development in Drosophila melanogaster*
,§,
, and**
Department of Pediatrics, Section of
Respiratory Medicine, ¶ Department of Psychiatry, Howard
Hughes Medical Institute, Department of Genetics and Boyer Center for
Molecular Medicine, and the ** Department of Cellular and
Molecular Physiology, Yale University School of Medicine,
New Haven, Connecticut 06520
*
This work was supported by Grants PO1-NICHD32573,
RO1-NS35918, and RO1-HL66327 from the National Institutes of Health (to G. G. H.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Dept.
of Pediatrics, Section of Respiratory Medicine, Yale University School
of Medicine, Fitkin Memorial Pavilion, Rm. 506, 333 Cedar St., New Haven, CT 06520; Tel.: 203-785-5444; Fax: 203-785-6337; E-mail: Gabriel.haddad@yale.edu.
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