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Restoration of SERCA ATPase Prevents Oxidative Stress-Related Muscle Atrophy and Weakness

Restoration of SERCA ATPase Prevents Oxidative Stress-Related Muscle Atrophy and Weakness

Rizwan Qaisar, Shylesh Bhaskaran, Rojina Ranjit, Kavithalakshmi Sataranatarajan, Pavithra Premkumar, Kendra Huseman, Holly Van Remmen

Redox Biol. 2019 Jan;20:68-74.

PMID: 30296699

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP892711750	CDN1163		892711-75-0	Price

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