Exercise-induced skeletal muscle EcSOD in disease protection
Exercise training is the most effective intervention against numerous diseases, including cancer, cardiovascular, metabolic and neurodegenerative diseases; however, the underlying mechanisms are not fully understood. The Yan Lab has obtained data to show that a secreted antioxidant protein, extracellular superoxide dismutase (EcSOD), is highly induced in skeletal muscle by endurance exercise training. The team hypothesizes that endurance exercise training-induced EcSOD expression in skeletal muscle provides protection against oxidative damage in skeletal muscle and other peripheral tissues/organs against various disease conditions. The lab is specifically interested in the roles of endurance exercise training-induced EcSOD expression in protection against catabolic muscle wasting, diabetic cardiomyopathy and multiple organ dysfunction syndrome induced by endotoxemia, sepsis and trauma. The findings will provide novel insights into the moledular mechanism by which regular exercise elicits profound protection against many other disease conditions, such as diabetes, atherosclerosis, heart failure and peripheral arterial disease.
Publications
Li P, Waters RE, Redfern SI, Zhang M, Mao L, Annex BH, Yan Z. Oxidative phenotype protects myofibers from pathological insults induced by chronic heart failure in mice. Am. J. Pathol. 2007; 170(2):599-608.
Yu Z, Li P, Zhang M, Hannink M, Stamler JS, Yan Z. Fiber type-specific nitric oxide protects oxidative myofibers against cachectic stimuli. PLoS One 3(5): e2086, 2008.
Geng T, Li P, Yin X, Yan Z. PGC-1α Promotes Nitric Oxide Antioxidant Defenses and Inhibits FOXO Signaling Against Cardiac Cachexia in Mice. Am J Pathol. 2011 Apr;178(4):1738-48. PubMed PMID: 21435455. Link
Okutsu M, Call JA, Lira VA, Zhang M, Donet JA, French BA, Martin KS, Peirce-Cottler SM, Rembold CM, Annex BH, Yan Z. Extracellular Superoxide Dismutase Ameliorates Skeletal Muscle Abnormalities, Cachexia and Exercise Intolerance in Mice with Congestive Heart Failure. Circ Heart Fail. 2014 Feb 12. [Epub ahead of print] PubMed PMID: 24523418 .
Call JA, Chain KH, Martin KS, Lira VA, Okutsu M, Zhang M, Yan Z. Enhanced Skeletal Muscle Expression of EcSOD Mitigates Streptozotocin-Induced Diabetic Cardiomyopathy by Reducing Oxidative Stress and Aberrant Cell Signaling. Circ Heart Fail. 2014 PubMed PMID: 25504759.
Leitner LM, Wilson RJ, Yan Z, Gödecke A. Reactive Oxygen Species/Nitric Oxide Mediated Inter-Organ Communication in Skeletal Muscle Wasting Diseases. Antioxid Redox Signal. 2017 May 1;26(13):700-717. PubMed PMID: 27835923; PubMed Central PMCID: PMC5421600.
Call JA, Donet J, Martin KS, Sharma AK, Chen X, Zhang J, Cai J, Galarreta CA, Okutsu M, Du Z, Lira VA, Zhang M, Mehrad B, Annex BH, Klibanov AL, Bowler RP, Laubach VE, Peirce SM, Yan Z. Muscle-derived extracellular superoxide dismutase inhibits endothelial activation and protects against multiple organ dysfunction syndrome in mice. Free Radic Biol Med. 2017 Dec;113:212-223. PubMed PMID: 28982599; PubMed Central PMCID: PMC5740866.
Yan Z, Spaulding HR. Extracellular superoxide dismutase, a molecular transducer of health benefits of exercise. Redox Biol. 2020 Mar 19;32:101508. doi: 10.1016/j.redox.2020.101508. [Epub ahead of print] Review. PubMed PMID: 32220789; PubMed Central PMCID: PMC7109453.
