SERCA1 protein expression in muscle of patients with Brody disease and Brody syndrome and in cultured human muscle fibers

Guglielmi, Valeria and Vattemi, Gaetano and Gualandi, Francesca and Voermans, Nicol C. and Marini, Matteo and Scotton, Chiara and Pegoraro, Elena and Oosterhof, Arie and Kósa, Magdolna and Zádor, Ernő and Valente, Enza Maria and De Grandis, Domenico and Neri, Marcella and Codemo, Valentina and Novelli, Antonio and Kuppevelt, Toin H. van and Dallapiccola, Bruno and Engelen, Baziel G. van (2013) SERCA1 protein expression in muscle of patients with Brody disease and Brody syndrome and in cultured human muscle fibers. MOLECULAR GENETICS AND METABOLISM, 13. pp. 162-169. ISSN 1096-7192

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Brody disease is an inherited myopathy associated with a defective function of sarcoplasmic/endoplasmic reticulum Ca2+-ATPase 1 (SERCA1) protein. Mutations in the ATP2A1 gene have been reported only in some patients. Therefore it has been proposed to distinguish patients with ATP2A1 mutations, Brody disease (BD), from patients without mutations, Brody syndrome (BS). We performed a detailed study of SERCA1 protein expression in muscle of patients with BD and BS, and evaluated the alternative splicing of SERCA1 in primary cultures of normal human muscle and in infant muscle. SERCA1 reactivity was observed in type 2 muscle fibers of patients with and without ATP2A1 mutations and staining intensity was similar in patients and controls. Immunoblot analysis showed a significant reduction of SERCA1 band in muscle of BD patients. In addition we demonstrated that the wild type and mutated protein exhibits similar solubility properties and that RIPA buffer improves the recovery of the wild type and mutated SERCA1 protein. We found that SERCA1b, the SERCA1 neonatal form, is the main protein isoform expressed in cultured human muscle fibers and infant muscle. Finally, we identified two novel heterozygous mutations within exon 3 of the ATP2A1 gene from a previously described patient with BD.

Item Type: Article
Uncontrolled Keywords: Brody disease, Sarcoplasmic/endoplasmic reticulum Ca2+-, ATPase 1 (SERCA1),Brody syndrome, ATP2A1 gene
Subjects: Q Science / természettudomány > QH Natural history / természetrajz > QH301 Biology / biológia > QH3011 Biochemistry / biokémia
R Medicine / orvostudomány > R1 Medicine (General) / orvostudomány általában
Depositing User: MTMT SWORD
Date Deposited: 06 Sep 2013 08:32
Last Modified: 09 Sep 2013 08:19

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