Stability of mitochondrial DNA against reactive oxygen species (ROS) generated in diabetes.
Diabetes Metab Res Rev
; 27(5): 470-9, 2011 Jul.
Article
en En
| MEDLINE
| ID: mdl-21484980
ABSTRACT
BACKGROUND:
Increased production of reactive oxygen species (ROS) in mitochondria has been proposed as the pathogenic mechanism for chronic complications of diabetes. Mitochondrial DNA (mtDNA) is more vulnerable to reactive oxygen species. However, there are few data on the mitochondrial DNA damage in diabetes and these are available only from patients with different duration of the disease and tissues not relevant to the chronic complications of diabetes. We therefore proposed to study the stability of mitochondrial DNA under controlled experimental conditions, to understand its contribution to chronic complications of diabetes.METHODS:
The mitochondrial DNA damage was evaluated by long-fragment polymerase chain reaction in human dermal fibroblasts exposed to high glucose level and hypoxia (an additional source of reactive oxygen species) or in organs from diabetic animals (db/db mice) at different ages. Reactive oxygen species production was assessed in vitro by fluorescence and in vivo by nitrosylation of the proteins. The antioxidant enzymes were assessed by enzyme activity and by quantitative real-time polymerase chain reaction while the mitochondrial repair activity (base excision repair) was determined by using abasic site-containing oligonucleotides as substrates.RESULTS:
Hyperglycaemia, when combined with hypoxia, is able to induce mitochondrial DNA damage in human dermal fibroblasts. The deleterious effect is mediated by mitochondrial reactive oxygen species, being abolished when the mitochondria electron transport is blocked. The accumulation of mitochondrial DNA damage in vivo is, however, decreased in 'old' diabetic animals (db/db) despite higher reactive oxygen species levels. This mitochondrial DNA protection might be conferred by an increased base excision repair activity.CONCLUSION:
Increased base excision repair activity in tissues affected by the chronic complications of diabetes is a potential mechanism that can overcome mitochondrial DNA damage induced by hyperglycaemia-related reactive oxygen species overproduction.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
ADN Mitocondrial
/
Especies Reactivas de Oxígeno
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Diabetes Metab Res Rev
Asunto de la revista:
ENDOCRINOLOGIA
/
METABOLISMO
Año:
2011
Tipo del documento:
Article
País de afiliación:
Suecia