Počet záznamů: 1
Deterioration of mitochondrial bioenergetics and ultrastructure impairment in skeletal muscle of a transgenic minipig model in the early stages of Huntington's disease
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SYSNO ASEP 0512108 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Deterioration of mitochondrial bioenergetics and ultrastructure impairment in skeletal muscle of a transgenic minipig model in the early stages of Huntington's disease Tvůrce(i) Rodinová, M. (CZ)
Křížová, J. (CZ)
Štufková, H. (CZ)
Bohuslavová, Božena (UZFG-Y) ORCID
Askeland, G. (NO)
Dosoudilová, Z. (CZ)
Juhás, Štefan (UZFG-Y) RID, ORCID
Juhásová, Jana (UZFG-Y) RID, ORCID
Ellederová, Zdeňka (UZFG-Y) RID, ORCID
Zeman, J. (CZ)
Eide, L. (NO)
Motlík, Jan (UZFG-Y) RID, ORCID
Hansíková, H. (CZ)Číslo článku dmm038737 Zdroj.dok. Disease Models & Mechanisms. - : Company of Biologists - ISSN 1754-8403
Roč. 12, č. 7 (2019)Poč.str. 11 s. Forma vydání Online - E Jazyk dok. eng - angličtina Země vyd. GB - Velká Británie Klíč. slova Huntington´s disease ; mitochondrial function ; ultrastructure ; HD large animal model Vědní obor RIV EB - Genetika a molekulární biologie Obor OECD Cell biology CEP LO1609 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy 7F14308 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy Způsob publikování Open access Institucionální podpora UZFG-Y - RVO:67985904 UT WOS 000478759400005 DOI 10.1242/dmm.038737 Anotace Skeletal muscle wasting and atrophy is one of the more severe clinical impairments resulting from the progression of Huntington's disease (HD). Mitochondrial dysfunction may play a significant role in the etiology of HD, but the specific condition of mitochondria in muscle has not been widely studied during the development of HD. To determine the role of mitochondria in skeletal muscle during the early stages of HD, we analyzed quadriceps femoris muscle from 24-, 36-, 48- and 66-month-old transgenic minipigs that expressed the N-terminal portion of mutated human huntingtin protein (TgHD) and age-matched wild-type (WT) siblings. We found altered ultrastructure of TgHD muscle tissue and mitochondria. There was also significant reduction of activity of citrate synthase and respiratory chain complexes (RCCs) I, II and IV, decreased quantity of oligomycin-sensitivity conferring protein (OSCP) and the E2 subunit of pyruvate dehydrogenase (PDHE2), and differential expression of optic atrophy 1 protein (OPA1) and dynamin-related protein 1 (DRP1) in the skeletal muscle of TgHD minipigs. Statistical analysis identified several parameters that were dependent only on HD status and could therefore be used as potential biomarkers of disease progression. In particular, the reduction of biomarker RCCII subunit SDH30 quantity suggests that similar pathogenic mechanisms underlie disease progression in TgHD minipigs and HD patients. The perturbed biochemical phenotype was detectable in TgHD minipigs prior to the development of ultrastructural changes and locomotor impairment, which become evident at the age of 48 months. Mitochondrial disturbances may contribute to energetic depression in skeletal muscle in HD, which is in concordance with the mobility problems observed in this model. Pracoviště Ústav živočišné fyziologie a genetiky Kontakt Jana Zásmětová, knihovna@iapg.cas.cz, Tel.: 315 639 554 Rok sběru 2020 Elektronická adresa https://dmm.biologists.org/content/12/7/dmm038737
Počet záznamů: 1