Neuron specific reduction in CuZnSOD is not sufficient to initiate a full sarcopenia phenotype

Collapse authors list.
Sataranatarajan, Kavithalakshmi, Qaisar, Rizwan, Davis, Carol, Sakellariou, George, Vasilaki, Aphrodite ORCID: 0000-0002-5652-0895, Zhang, Yiqiang, Liu, Yuhong, Bhaskaran, Shylesh, McArdle, Anne, Jackson, Malcolm ORCID: 0000-0003-3683-8297 et al (show 3 more authors) , Brooks, Susan V, Richardson, Arlan and Van Remmen, Holly (2015) Neuron specific reduction in CuZnSOD is not sufficient to initiate a full sarcopenia phenotype. Redox Biology, 5. pp. 140-148.

Text pdf for nko paper.pdf - Author Accepted Manuscript Download (984kB)

Abstract

Our previous studies showed that adult (8 month) mice lacking CuZn-superoxide dismutase (CuZnSOD, Sod1KO mice) have neuromuscular changes resulting in dramatic accelerated muscle atrophy and weakness that mimics age-related sarcopenia. We have further shown that loss of CuZnSOD targeted to skeletal muscle alone results in only mild weakness and no muscle atrophy. In this study we targeted deletion of CuZnSOD specifically to neurons (nSod1KO mice) and determined the effect on muscle mass and weakness. The nSod1KO mice show a significant loss of CuZnSOD activity and protein level in brain and spinal cord but not in muscle tissue. The masses of the gastrocnemius, tibialis anterior and extensor digitorum longus (EDL) muscles were not reduced in nSod1KO compared to wild type mice, even at 20 months of age, although the quadriceps and soleus muscles showed small but significant reductions in mass in the nSod1KO mice. Maximum isometric specific force was reduced 8% to 10% in the gastrocnemius and EDL muscle of nSod1KO mice, while soleus was not affected. Muscle mitochondrial ROS generation and oxidative stress measured by levels of reactive oxygen/nitrogen species (RONS) regulatory enzymes, protein nitration and F2-isoprostane levels were not increased in muscle from the nSod1KO mice. Although we did not find evidence of denervation in the nSOD1KO mice, neuromuscular junction morphology was altered and the expression of genes associated with denervation (acetylcholine receptor subunit alpha (AChRα) and the transcription factors Runx1 and GADD45α) was increased, supporting a role for neuronal loss of CuZnSOD initiating alterations at the neuromuscular junction. These results and our previous studies support the concept that deficits in either the motor neuron or muscle alone are not sufficient to initiate a full sarcopenic phenotype and that deficits in both tissues are required to recapitulate the loss of muscle observed in Sod1KO mice.

Item Type:	Article
Additional Information:	Cite as: Kavithalakshmi Sataranatarajan, Rizwan Qaisar, Carol Davis, Giorgos K. Sakellariou, Aphrodite Vasilaki, Yiqiang Zhang, Yuhong Liu, Shylesh Bhaskaran, Anne McArdle, Malcolm Jackson, Susan V. Brooks, Arlan Richardson and Holly Van Remmen, Neuron specific reduction in CuZnSOD is not sufficient to initiate a full sarcopenia phenotype, Redox Biology, http://dx.doi.org/10.1016/j.redox.2015.04.005
Uncontrolled Keywords:	CuZnSOD, Oxidative stress, neuromuscular junction, muscle atrophy, sarcopenia
Depositing User:	Symplectic Admin
Date Deposited:	21 Apr 2015 15:02
Last Modified:	15 Dec 2022 11:47
DOI:	10.1016/j.redox.2015.04.005
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/2010326