Restoration of SERCA ATPase prevents oxidative stress-related muscle atrophy and weakness.

Autor:	Qaisar R; Aging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA., Bhaskaran S; Aging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA., Ranjit R; Aging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA., Sataranatarajan K; Aging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA., Premkumar P; Aging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA., Huseman K; Aging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA., Van Remmen H; Aging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA; Oklahoma City VA Medical Center, Oklahoma City, OK 73104, USA. Electronic address: Holly-VanRemmen@omrf.org.
Jazyk:	angličtina
Zdroj:	Redox biology [Redox Biol] 2019 Jan; Vol. 20, pp. 68-74. Date of Electronic Publication: 2018 Sep 27.
DOI:	10.1016/j.redox.2018.09.018
Abstrakt:	Molecular targets to reduce muscle weakness and atrophy due to oxidative stress have been elusive. Here we show that activation of Sarcoplasmic Reticulum (SR) Ca 2+ 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. (Published by Elsevier B.V.)
Databáze:	MEDLINE
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