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Method and compositions for altering cell function

A composition and cathepsin technology, which can be used in drug combinations, pharmaceutical formulations, plant raw materials, etc., and can solve problems such as dangerous toxicity and reversal of beneficial effects.

Active Publication Date: 2007-11-21
ALLTECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, at elevated dose levels, the beneficial effects were reversed and dangerous toxicity was shown

Method used

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  • Method and compositions for altering cell function
  • Method and compositions for altering cell function
  • Method and compositions for altering cell function

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0321] Materials and methods

[0322] animal management. Male C57BL / 6J mice were housed individually, and the following experimental diets were started immediately after weaning (21 days old). Mice were housed at the Shared Aging Rodent Facility at William S. Middleton Memorial Veterans Administration Medical Center (Madison WI). Temperature and humidity are kept at constant levels. Control interior lighting to provide a 12-hour light-dark cycle.

[0323] Experimental diets were manufactured by Harlan Teklad (Madison WI). The selenium content of the feed was determined by Covance Inc. (Madison WI). Five animals were included in each of the following treatment groups: selenium-deficient diet (SD); diet supplemented with selenomethionine (SM, obtained from Sigma, St.Louis, MO), the final selenium concentration in this diet was parts per million Parts per million; feed supplemented with sodium selenite (SS, Sigma), where the final selenium content i...

Embodiment 2

[0345] Dietary selenium alters gene expression in mouse gut

[0346] In the mouse gut and brain (e.g., cerebral cortex), dietary selenium (e.g., from various sources such as SeM, Sel-sod, and Sel-Plex) has been examined to alter physiology (e.g., physiological homeostasis) and expression patterns of various protein functional groups and various protein pathways (eg, expression patterns of proteins or genes).

[0347] Accordingly, it was an object of the present invention to determine whether the compositions and methods of the present invention alter the expression levels (eg, mRNA levels) of various genes. The set of genes analyzed is those typically associated with selenium. Gene expression levels were analyzed between mice supplemented with and without dietary selenium, or between mice fed different sources of selenium, as described above (see, eg, Table 1 below). When receiving selenium-deficient feed, feed containing selenomethionine (Se-meth, or SeM),...

Embodiment 3

[0354] Dietary selenium alters the expression levels of selenoprotein-encoding genes in a selenium-source-dependent manner

[0355] It is now known that selenium is incorporated into many selenoproteins in the form of selenocysteine, glutathione peroxidase (GSH-Px, see Example 2) is a typical example. Selenocysteine ​​is specifically encoded by the UGA codon and is inserted into the polypeptide chain by a co-translational mechanism that overrides the normal function of UGA as a stop codon. In eukaryotes, efficient incorporation of selenocysteine ​​at UGA codon positions requires cellular protein factors and a cis-acting structural signal usually localized in the 3'-untranslated region (3'-UTR) of mRNA, which The cis-acting signal consists of a selenocysteine ​​insertion sequence (SECIS) in a characteristic stem-loop structure (see, e.g., Peterlin, et al. (1993), In Human Retroviruses; Cullen, Ed.; Oxford University Press: New York ; pp. 75-100; Le and Maizel, Theor. Biol. 138...

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Abstract

The present invention relates to compositions and methods for altering cell function. In particular, the present invention provides compositions comprising selenium (e.g., Sel-Plex) and methods of using the same (e.g., as a therapeutic and / or prophylactic treatment for neurodegenerative disease). Additionally, the present invention demonstrates that specific forms of selenium (e.g., Sel-Plex) possess the ability to alter expression of genes associated with disease and / or aging while other forms of selenium (e.g., selenomethionine) do not.

Description

field of invention [0001] The present invention relates to methods and compositions for altering cellular function. Specifically, the present invention provides selenium-containing (eg, Sel-Plex) compositions and methods of their use (eg, for the therapeutic and / or prophylactic treatment of neurodegenerative diseases). In addition, the present invention demonstrates that certain forms of selenium (eg, Sel-Plex) can alter the expression of genes associated with disease and / or aging. Background technique [0002] Selenium is an essential trace element for normal physiological functions of the human body. People get selenium from their diet, which can have varying amounts of selenium. For example, in most parts of the world, crops are grown that are low in selenium because of low levels of selenium in the soil. [0003] Selenium is incorporated into various organic molecules including, for example, amino acids such as 1-selenomethionine, selenocysteine ​​and selenocystine. ...

Claims

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Application Information

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IPC IPC(8): A61K36/064A61K33/06A61K45/00A61P25/28A61P25/14A61P25/16A61P3/10
CPCA61K45/06A61K38/28A61K33/04A61P25/00A61P25/14A61P25/16A61P25/28A61P3/10A61P43/00A61K2300/00
Inventor T·P·莱昂斯R·鲍尔
Owner ALLTECH CO LTD
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