Document Detail


Medical bioremediation: a concept moving toward reality.
MedLine Citation:
PMID:  20041735     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Abstract A major driver of aging is catabolic insufficiency, the inability of our bodies to break down certain substances that accumulate slowly throughout the life span. Even though substance buildup is harmless while we are young, by old age the accumulations can reach a toxic threshold and cause disease. This includes some of the most prevalent diseases in old age-atherosclerosis and macular degeneration. Atherosclerosis is associated with the buildup of cholesterol and its oxidized derivatives (particularly 7-ketocholesterol) in the artery wall. Age-related macular degeneration is associated with carotenoid lipofuscin, primarily the pyridinium bisretinoid A2E. Medical bioremediation is the concept of reversing the substance accumulations by using enzymes from foreign species to break down the substances into forms that relieve the disease-related effect. We report on an enzyme discovery project to survey the availability of microorganisms and enzymes with these abilities. We found that such microorganisms and enzymes exist. We identified numerous bacteria having the ability to transform cholesterol and 7-ketocholesterol. Most of these species initiate the breakdown by same reaction mechanism as cholesterol oxidase, and we have used this enzyme directly to reduce the toxicity of 7-ketocholesterol, the major toxic oxysterol, to cultured human cells. We also discovered that soil fungi, plants, and some bacteria possess peroxidase and carotenoid cleavage oxygenase enzymes that effectively destroy with varied degrees of efficiency and selectivity the carotenoid lipofuscin found in macular degeneration.
Authors:
John Schloendorn; Tim Webb; Kent Kemmish; Mark Hamalainen; David Jackemeyer; Lijing Jiang; Jacques Mathieu; Justin Rebo; Jonathan Sankman; Lindsey Sherman; Lauri Tontson; Ateef Qureshi; Pedro Alvarez; Bruce Rittmann
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Rejuvenation research     Volume:  12     ISSN:  1557-8577     ISO Abbreviation:  Rejuvenation Res     Publication Date:  2009 Dec 
Date Detail:
Created Date:  2009-12-31     Completed Date:  2010-03-03     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101213381     Medline TA:  Rejuvenation Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  411-9     Citation Subset:  IM    
Affiliation:
Biodesign Institute at Arizona State University, Tempe, Arizona, USA. zauberkugel@gmail.com
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MeSH Terms
Descriptor/Qualifier:
Biotransformation* / drug effects
Carotenoids / chemistry,  metabolism
Cell Line
Cholesterol Oxidase / metabolism
Chromatography, Liquid
Environmental Microbiology
Esters / chemistry,  metabolism
Humans
Hydrolysis / drug effects
Isotope Labeling
Ketocholesterols / chemistry,  metabolism
Mass Spectrometry
Oxygenases / metabolism
Peroxidases / metabolism
Pyridinium Compounds / chemistry,  metabolism
Retinoids / chemistry,  metabolism
Sterols / chemistry,  metabolism,  toxicity
Chemical
Reg. No./Substance:
0/A2E compound; 0/Esters; 0/Ketocholesterols; 0/Pyridinium Compounds; 0/Retinoids; 0/Sterols; 36-88-4/Carotenoids; 566-28-9/7-ketocholesterol; EC 1.1.3.6/Cholesterol Oxidase; EC 1.11.1.-/Peroxidases; EC 1.13.-/Oxygenases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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