Shortening of telomere length by metabolic factors in diabetes: protective effects of fenofibrate.
J Cell Commun Signal
; 13(4): 523-530, 2019 Dec.
Article
en En
| MEDLINE
| ID: mdl-31203557
ABSTRACT
People with diabetes mellitus have shorter telomeres compared with non-diabetic subjects. The aim of this study was to investigate an in-vitro model of telomere shortening under diabetes metabolic conditions. The mechanisms of the accelerated telomere length attrition and the potential telomere protective action of fenofibrate with related cellular mechanisms were also examined. Human dermal fibroblasts were passaged and cultured in normal (5.5 mM) or high (25 mM) D-glucose, across 7 days with hydrogen peroxide (H2O2), glucosamine (GA), or glycated albumin (AGEs-BSA). Relative telomere length (RTL) was determined by qPCR. The expression of shelterin complex members which regulate telomere stability were measured by qRT-PCR and Western immunoblot. Culture in high glucose decreased RTL compared with normal glucose H2O2 and GA lowered the RTL after 7 days (each P < 0.05 vs untreated control), whereas AGEs-BSA had no effect compared with control-BSA. At day 7 the mRNA levels of most shelterin complex members, were induced by H2O2 and to a lesser extent by GA. Trf1 and Trf2 protein were induced by H2O2. Co-treatment with fenofibrate (100 µM) significantly attenuated the reduction in RTL caused by H2O2 and GA and prevented Trf induction by H2O2. However knockdown of Trf1 and Trf2 expression using specific siRNA did not prevent H2O2 effects to lower RTL, thus implicating factors other than these Trfs alone in the fenofibrate protection against the H2O2 induction of RTL lowering. These in vitro findings demonstrate that diabetic conditions can induce telomere shortening and that fenofibrate has protective effects on telomere attrition, through as yet undefined mechanisms.
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Base de datos:
MEDLINE
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
J Cell Commun Signal
Año:
2019
Tipo del documento:
Article