Age-Related Oxidative Changes in Primary Porcine Fibroblasts Expressing Mutated Huntingtin

• DOI: 10.1159/000500091
• Publication Date: 2019-06-05T21:00:33Z
• Authors: Petra Smatlikova; Georgina Askeland; Michaela Vaskovicova; Jiri Klima; Jan Motlik; Lars Eide; Zdenka Ellederová
• Keywords: SOD2

<b><i>Background:</i></b> Huntington’s disease (HD) is a devastating neurodegenerative disorder caused by CAG triplet expansions in the huntingtin gene. Oxidative stress linked to HD pathology, although it not clear whether this an effect or mediator of disease. The transgenic (TgHD) minipig expresses N-terminal part human-mutated and represents unique model investigate therapeutic strategies towards HD. A more detailed characterization needed fully utilize its potential. <b><i>Methods:</i></b> In study, we focused on molecular cellular features fibroblasts isolated from TgHD minipigs wild-type (WT) siblings at different ages, pre-symptomatic age 24–36 months with onset behavioural symptoms 48 months. We measured oxidative stress, expression stress-related genes, proliferation capacity along cyclin B1 D1 proteins, permeability, integrity nuclear DNA (nDNA) mitochondrial these cells. <b><i>Results:</i></b> 48-month-old animals showed increased which correlated overexpression <i>SOD2</i> encoding superoxide dismutase 2, <i>NEIL3</i> gene glycosylase involved replication-associated repair oxidized DNA. cells displayed abnormal permeability. further demonstrated nDNA damage (isolated aged months). <b><i>Conclusions:</i></b> Our results unravel phenotypic alterations primary Importantly, appears precede alterations. highlight impact studying mechanisms pathophysiology that gradually occur age.