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dc.contributor.authorFajardo, Val Andrew
dc.contributor.authorTrojanowski, Natalie S.
dc.contributor.authorCastelli, Laura
dc.contributor.authorMiotto, Paula
dc.contributor.authorAmoye, Foyinsola
dc.contributor.authorWard, Wendy E.
dc.contributor.authorTupling, A. Russell
dc.contributor.authorLeBlanc, Paul
dc.date.accessioned2017-02-17T16:17:56Z
dc.date.available2017-02-17T16:17:56Z
dc.date.issued2017-01-26
dc.identifier.urihttp://hdl.handle.net/10464/10976
dc.description.abstractThe sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) pumps are integral membrane proteins that catalyze the active transport of Ca2+ into the sarcoplasmic reticulum, thereby eliciting muscle relaxation. SERCA pumps are highly susceptible to oxidative damage, and cytoprotection of SERCA dampens thermal inactivation and is a viable therapeutic strategy in combating diseases where SERCA activity is impaired, such as muscular dystrophy. Here, we sought to determine whether increasing the percent of saturated fatty acids (SFA) within SERCA's lipid annulus through diet could protect SERCA pumps from thermal inactivation. Female Wistar rats were fed either a semi-purified control diet (AIN93G, 7% soybean oil by weight) or a modified AIN93G diet containing high SFA (20% lard by weight) for 17 weeks. Soleus muscles were extracted and SERCA lipid annulus and activity under thermal stress were analyzed. Our results show that SERCA's lipid annulus is abundant with short-chain (12–14 carbon) fatty acids, which corresponds well with SERCA's predicted bilayer thickness of 21 Å. Under control-fed conditions, SERCA's lipid annulus was already highly saturated (79%), and high-fat feeding did not increase this any further. High-fat feeding did not mitigate the reductions in SERCA activity seen with thermal stress; however, correlational analyses revealed significant and strong associations between % SFA and thermal stability of SERCA activity with greater %SFA being associated with lower thermal inactivation and greater % polyunsaturation and unsaturation index being associated with increased thermal inactivation. Altogether, these findings show that SERCA's lipid annulus may influence its susceptibility to oxidative damage, which could have implications in muscular dystrophy and age-related muscle wasting.en_US
dc.description.sponsorshipAnalyses supported by a Discovery Grant from the Natural Sciences and Engineering Research Council of Canada to PJL. The in vivo portion of the study was funded by start-up funding from Brock University to WEW. VAF was supported through a Canadian Institutes of Health Research (CIHR) Doctoral Award; NT and PM were both supported through CIHR Master's Awards; LC was supported through an Ontario Graduate Scholarship. WEW holds a Canada Research Chair in Bone and Muscle Development.en_US
dc.language.isoenen_US
dc.publisherElsevieren_US
dc.rightsAttribution-NonCommercial-NoDerivs 2.5 Canada*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/2.5/ca/*
dc.subjectHigh fat dieten_US
dc.subjectSaturated fatsen_US
dc.subjectMonounsaturated fatsen_US
dc.subjectPolyunsaturated fatsen_US
dc.subjectHeat stressen_US
dc.titleSaturation of SERCA's lipid annulus may protect against its thermal inactivation.en_US
dc.typeArticleen_US
dc.identifier.doihttp://dx.doi.org/10.1016/j.bbrc.2017.01.154
refterms.dateFOA2017-02-17T00:00:00Z


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