title: Saturation of SERCA's lipid annulus may protect against its thermal inactivation.
abstract: The 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.
authors.affiliation: Department of Kinesiology, University of Waterloo, Waterloo, ON, Canada; Center for Bone and Muscle Health, Brock University, St. Catharines, ON, Canada; Department of Health Sciences, Brock University, St. Catharines, ON, Canada.
authors.forename: Val Andrew
authors.initials: VA
authors.lastname: Fajardo
authors.affiliation: Center for Bone and Muscle Health, Brock University, St. Catharines, ON, Canada; Department of Health Sciences, Brock University, St. Catharines, ON, Canada.
authors.forename: Natalie
authors.initials: N
authors.lastname: Trojanowski
authors.affiliation: Center for Bone and Muscle Health, Brock University, St. Catharines, ON, Canada; Department of Kinesiology, Brock University, St. Catharines, ON, Canada.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Castelli
authors.affiliation: Center for Bone and Muscle Health, Brock University, St. Catharines, ON, Canada; Department of Kinesiology, Brock University, St. Catharines, ON, Canada.
authors.forename: Paula M
authors.initials: PM
authors.lastname: Miotto
authors.affiliation: Center for Bone and Muscle Health, Brock University, St. Catharines, ON, Canada; Department of Health Sciences, Brock University, St. Catharines, ON, Canada.
authors.forename: Foyinsola
authors.initials: F
authors.lastname: Amoye
authors.affiliation: Center for Bone and Muscle Health, Brock University, St. Catharines, ON, Canada; Department of Health Sciences, Brock University, St. Catharines, ON, Canada; Department of Kinesiology, Brock University, St. Catharines, ON, Canada.
authors.forename: Wendy E
authors.initials: WE
authors.lastname: Ward
authors.affiliation: Department of Kinesiology, University of Waterloo, Waterloo, ON, Canada; Center for Bone and Muscle Health, Brock University, St. Catharines, ON, Canada.
authors.forename: A Russell
authors.initials: AR
authors.lastname: Tupling
authors.affiliation: Center for Bone and Muscle Health, Brock University, St. Catharines, ON, Canada; Department of Health Sciences, Brock University, St. Catharines, ON, Canada. Electronic address: pleblanc@brocku.ca.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: LeBlanc
mesh_terms: D000818:Animals; D005260:Female; D018869:Heat-Shock Response; D050356:Lipid Metabolism; D018482:Muscle, Skeletal / Q000201:enzymology; D051381:Rats; D017208:Rats, Wistar; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism*
chemical_list: D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases
keywords: Heat stress; High fat diet; Monounsaturated fats; Polyunsaturated fats; Saturated fats