title: Regulation of myokine expression: Role of exercise and cellular stress.
abstract: Exercise training is well known to improve physical fitness and to combat chronic diseases and aging related disorders. Part of this is thought to be mediated by myokines, muscle derived secretory proteins (mainly cytokines) that elicit auto/paracrine but also endocrine effects on organs such as liver, adipose tissue, and bone. Today, several hundred potential myokines have been identified most of them not exclusive to muscle cells. Strenuous exercise is associated with increased production of free radicals and reactive oxidant species (ROS) as well as endoplasmic reticulum (ER)-stress which at an excessive level can lead to muscle damage and cell death. On the other hand, transient elevations in oxidative and ER-stress are thought to be necessary for adaptive improvements by regular exercise through a hormesis action termed mitohormesis since mitochondria are essential for the generation of energy and tightly connected to ER- and oxidative stress. Exercise induced myokines have been identified by various in vivo and in vitro approaches and accumulating evidence suggests that ROS and ER-stress linked pathways are involved in myokine induction. For example, interleukin (IL)-6, the prototypic exercise myokine is also induced by oxidative and ER-stress. Exercise induced expression of some myokines such as irisin and meteorin-like is linked to the transcription factor PGC-1α and apparently not related to ER-stress whereas typical ER-stress induced cytokines such as FGF-21 and GDF-15 are not exercise myokines under normal physiological conditions. Recent technological advances have led to the identification of numerous potential new myokines but for most of them regulation by oxidative and ER-stress still needs to be unraveled.
authors.affiliation: Research Group Physiology of Energy Metabolism, German Institute of Human Nutrition in Potsdam Rehbrücke, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany.
authors.forename: Mario
authors.initials: M
authors.lastname: Ost
authors.affiliation: Research Group Physiology of Energy Metabolism, German Institute of Human Nutrition in Potsdam Rehbrücke, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany.
authors.forename: Verena
authors.initials: V
authors.lastname: Coleman
authors.affiliation: Research Group Physiology of Energy Metabolism, German Institute of Human Nutrition in Potsdam Rehbrücke, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany.
authors.forename: Juliane
authors.initials: J
authors.lastname: Kasch
authors.affiliation: Research Group Physiology of Energy Metabolism, German Institute of Human Nutrition in Potsdam Rehbrücke, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany. Electronic address: klaus@dife.de.
authors.forename: Susanne
authors.initials: S
authors.lastname: Klaus
mesh_terms: D059865:Endoplasmic Reticulum Stress; D015444:Exercise / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D009124:Muscle Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D018482:Muscle, Skeletal / Q000378:metabolism*; D018384:Oxidative Stress
chemical_list: D009124:Muscle Proteins
keywords: Endoplasmic reticulum; Exercise; FGF21; Integrated stress response; Mitochondrial disease; Myokine; Secretory proteins; Skeletal muscle