Journal
REDOX BIOLOGY
Volume 20, Issue -, Pages 68-74Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.redox.2018.09.018
Keywords
CDN1163; Skeletal muscle; CuZnSod1; SERCA; Oxidative stress
Categories
Funding
- Irene Diamond Fund/AFAR Postdoctoral Transition Award in Aging
- NIH [AG051442-020]
- Senior VA Research Career Scientist Award from the Department of Veterans Affairs
- NATIONAL INSTITUTE ON AGING [R01AG050676, P01AG051442] Funding Source: NIH RePORTER
- Veterans Affairs [I01BX002595] Funding Source: NIH RePORTER
Ask authors/readers for more resources
Molecular targets to reduce muscle weakness and atrophy due to oxidative stress have been elusive. Here we show that activation of Sarcoplasmic Reticulum (SR) Ca2+ ATPase (SERCA) with CDN1163, a novel small molecule allosteric SERCA activator, ameliorates the muscle impairment in the CuZnSOD deficient (Sod1(-/-)) mouse model of oxidative stress. Sod1(-/-) mice are characterized by reduced SERCA activity, muscle weakness and atrophy, increased oxidative stress and mitochondrial dysfunction. Seven weeks of CDN1163 treatment completely restored SERCA activity and reversed the 23% reduction in gastrocnemius mass and 22% reduction in specific force in untreated Sod1(-/-) versus wild type mice. These changes were accompanied by restoration of autophagy protein markers to the levels found in wild-type mice. CDN1163 also reversed the increase in mitochondrial ROS generation and oxidative damage in muscle tissue from Sod1(-/-) mice. Taken together our findings suggest that the pharmacological restoration of SERCA is a promising therapeutic approach to counter oxidative stress-associated muscle impairment.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available