Heterozygous SOD2 deletion selectively impairs SERCA function in the soleus of female mice.
AuthorBraun, Jessica L
Messner, Holt N
Cleverdon, Riley E G
Baranowski, Ryan W
Hamstra, Sophie I
Geromella, Mia S
Stuart, Jeffrey A
Fajardo, Val A
Journal titlePhysiological reports
Publication Begin pagee15285
MetadataShow full item record
AbstractThe sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA) restores intracellular Ca2+ ([Ca2+ ]i ) to resting levels after muscle contraction, ultimately eliciting relaxation. SERCA pumps are highly susceptible to tyrosine (T)-nitration, impairing their ability to take up Ca2+ resulting in reduced muscle function and increased [Ca2+ ]i and cellular damage. The mitochondrial antioxidant enzyme, superoxide dismutase 2 (SOD2), converts superoxide radicals into less reactive H2 O2 . Heterozygous deletion of SOD2 (Sod2+/- ) in mice increases mitochondrial oxidative stress; however, the consequences of reduced SOD2 expression in skeletal and cardiac muscle, specifically the effect on SERCA pumps, has yet to be investigated. We obtained soleus, extensor digitorum longus (EDL), and left ventricle (LV) muscles from 6 to 7 month-old wild-type (WT) and Sod2+/- female C57BL/6J mice. Ca2+ -dependent SERCA activity assays were performed to assess SERCA function. Western blotting was conducted to examine the protein content of SERCA, phospholamban, and sarcolipin; and immunoprecipitation experiments were done to assess SERCA2a- and SERCA1a-specific T-nitration. Heterozygous SOD2 deletion did not alter SERCA1a or SERCA2a expression in the soleus or LV but reduced SERCA2a in the EDL compared with WT, though this was not statistically significant. Soleus muscles from Sod2+/- mice showed a significant reduction in SERCA's apparent affinity for Ca2+ when compared to WT, corresponding with significantly elevated SERCA2a T-nitration in the soleus. No effect was seen in the EDL or the LV. This is the first study to investigate the effects of SOD2 deficiency on muscle SERCA function and shows that it selectively impairs SERCA function in the soleus.
- Characterizing SERCA Function in Murine Skeletal Muscles after 35-37 Days of Spaceflight.
- Authors: Braun JL, Geromella MS, Hamstra SI, Messner HN, Fajardo VA
- Issue date: 2021 Oct 29
- The effects of neurogranin knockdown on SERCA pump efficiency in soleus muscles of female mice fed a high fat diet.
- Authors: Braun JL, Ryoo J, Goodwin K, Copeland EN, Geromella MS, Baranowski RW, MacPherson REK, Fajardo VA
- Issue date: 2022
- ATP consumption by sarcoplasmic reticulum Ca²⁺ pumps accounts for 40-50% of resting metabolic rate in mouse fast and slow twitch skeletal muscle.
- Authors: Smith IC, Bombardier E, Vigna C, Tupling AR
- Issue date: 2013
- The regulation of sarco(endo)plasmic reticulum calcium-ATPases (SERCA).
- Authors: Stammers AN, Susser SE, Hamm NC, Hlynsky MW, Kimber DE, Kehler DS, Duhamel TA
- Issue date: 2015 Oct
- Co-expression of SERCA isoforms, phospholamban and sarcolipin in human skeletal muscle fibers.
- Authors: Fajardo VA, Bombardier E, Vigna C, Devji T, Bloemberg D, Gamu D, Gramolini AO, Quadrilatero J, Tupling AR
- Issue date: 2013