Increased resistance to oxysterol cytotoxicity in fibroblasts transfected with a lysosomally targeted Chromobacterium oxidase.
Biotechnol Bioeng
; 109(9): 2409-15, 2012 Sep.
Article
em En
| MEDLINE
| ID: mdl-22447444
ABSTRACT
7-Ketocholesterol (7KC) is a cytotoxic oxysterol that plays a role in many age-related degenerative diseases. 7KC formation and accumulation often occurs in the lysosome, which hinders enzymatic transformations that reduce its toxicity and increase the sensitivity to lysosomal membrane permeabilization. We assayed the potential to mitigate 7KC cytotoxicity and enhance cell viability by overexpressing 7KC-active enzymes in human fibroblasts. One of the enzymes tested, a cholesterol oxidase engineered for lysosomal targeting, significantly increased cell viability in the short term upon treatment with up to 50 µM 7KC relative to controls. These results suggest targeting the lysosome for optimal treatment of oxysterol-mediated cytotoxicity, and support the use of introducing novel catalytic function into the lysosome for therapeutic and research applications.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Colesterol Oxidase
/
Chromobacterium
/
Substâncias Protetoras
/
Fibroblastos
/
Cetocolesteróis
Limite:
Humans
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article