Saturation of SERCA's lipid annulus may protect against its thermal inactivation
| Autor: | Laura M Castelli, Natalie Trojanowski, A. Russell Tupling, Wendy E. Ward, Val A. Fajardo, Foyinsola Amoye, Paul J. LeBlanc, Paula M. Miotto |
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| Rok vydání: | 2017 |
| Předmět: |
inorganic chemicals
0301 basic medicine medicine.medical_specialty animal structures SERCA Biophysics 030204 cardiovascular system & hematology Biochemistry Sarcoplasmic Reticulum Calcium-Transporting ATPases 03 medical and health sciences 0302 clinical medicine Internal medicine medicine Animals Rats Wistar Muscular dystrophy Muscle Skeletal Molecular Biology Annulus (mycology) Degree of unsaturation Chemistry musculoskeletal neural and ocular physiology Endoplasmic reticulum Cell Biology Lipid Metabolism medicine.disease Cytoprotection Rats 030104 developmental biology Muscle relaxation Endocrinology cardiovascular system Female tissues Reticulum Heat-Shock Response |
| Zdroj: | Biochemical and Biophysical Research Communications. 484:456-460 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2017.01.154 |
| Popis: | 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 A. 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. |
| Databáze: | OpenAIRE |
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