All-trans retinoic acid and rapamycin normalize Hutchinson Gilford progeria fibroblast phenotype.

ABSTRACT: Hutchinson Gilford progeria syndrome is a fatal disorder characterized by accelerated aging, bone resorption and atherosclerosis, caused by a LMNA mutation which produces progerin, a mutant lamin A precursor. Progeria cells display progerin and prelamin A nuclear accumulation, altered histone methylation pattern, heterochromatin loss, increased DNA damage and cell cycle alterations. Since the LMNA promoter contains a retinoic acid responsive element, we investigated if all-trans retinoic acid administration could lower progerin levels in cultured fibroblasts. We also evaluated the effect of associating rapamycin, which induces autophagic degradation of progerin and prelamin A. We demonstrate that all-trans retinoic acid acts synergistically with low-dosage rapamycin reducing progerin and p

SUBMITTER: Pellegrini C 

PROVIDER: S-EPMC4745772 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature