Valproic Acid Reduces Reactive Oxygen Species in Fibroblast of X-linked Adrenoleukodystrophy
강준원 ; 전철구 ; 강훈철 ; 장지호
Journal of the Korean Child Neurology Society (대한소아신경학회지)
Journal of the Korean Child Neurology Society (대한소아신경학회지), Vol.23(2) : 45~50, 2015
Purpose: X-linked adrenoleukodystrophy (X-ALD) is a fatal, axonal demyelinating, neurodegenerative disease, and is caused by mutations the in ABCD1 (ATP-binding cassette transporter subfamily D member 1). Oxidative damage of proteins caused by very long chain fatty acid accumulating in X-ALD, is an early event in the neuro-degenerative cascade. We evaluated valproic acid (VPA) as a possible option for oxidative damage in X-ALD.
Method: We generated fibroblast of the childhood cerebral ALD from patient. We evaluated mRNA (ribonucleic acid) level of ABCD2 by real-time polymerase chain reaction, and reactive oxygen species (ROS) levels by flow cytometry.
Results: VPA increased expression of ABCD2 in both control and ALD fibroblast. ABCD2 gene mRNA expression was increased 1.76 fold in normal fibroblasts, and 2.22 fold in the X-ALD fibroblasts. ROS levels were decreased in VPA treated X-ALD fibroblast, especially in treated with 1 mM of VPA. ROS levels revealed 13.7 in control fibroblast, on the other hand, 5.83 in X-ALD fibroblast treated with 1 mM of VPA.
Conclusion: We propose VPA as a promising novel therapeutic approach in oxidant damage that warrants further clinical investigation in X-ALD.